Global Institute Of Stem Cell Therapy And Research
US: +1 (800) 969-4188 | Mexico: +1 (619) 866-6000 | India: +91-8905483753

Category

Stem Cell News

Mesenchymal Stem Cell Conditioned Media Ameliorate Psoriasis Vulgaris: A Case Study

 

Seetharaman R, Mahmood A, Kshatriya P, Patel D, Srivastava A. Case Reports in Dermatological Medicine. May 2019; Article ID 8309103. https://doi.org/ 10.1155/ 2019/ 8309103.

Case Reports in Dermatological Medicine

Volume 2019, Article ID 8309103, 5 pages
https://doi.org/10.1155/2019/8309103
Case Report

Mesenchymal Stem Cell Conditioned Media Ameliorate Psoriasis Vulgaris: A Case Study

1GIOSTAR Research Inc. Pvt. Ltd., Ahmedabad, Gujrat, India
2Global Institute of Stem Cell Therapy and Research, 4660 La Jolla Village Drive, San Diego, CA 92122, USA

Correspondence should be addressed to Anand Srivastavaanand@giostar.com

Received 6 April 2019; Accepted 21 April 2019; Published 2 May 2019

Academic Editor: Jacek Cezary Szepietowski

Copyright © 2019 Rajasekar Seetharaman et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Psoriasis, an autoimmune disease, affects a vast number of peoples around the world. In this report, we discuss our findings about a scalp psoriasis suffering patient with a Psoriasis Scalp Severity Index (PSSI) score of 28, who was treated with Mesenchymal stem cell conditioned media (MSC-CM). Remarkably, complete regression was recorded within a treatment period of one month only (PSSI score of 0). A number of bioactive factors like cytokines and growth factors secreted by MSCs in the conditioned medium are very likely to be the principle molecules which play a vital role in skin regeneration. Treatment using MSC-CM appears to be an effective tool for tackling the psoriatic problem and, thus, may offer a new avenue of therapy which could be considered as an alternative approach to overcome the limitations of the cell-based therapy.

1. Introduction

Psoriasis is a chronic disease thought to be of autoimmune origin which is characterized by patches on the skin and nails. It has been considered as a serious skin related problem affecting approximately 100 million individuals worldwide. About 2% of the world population and 0.44-2.8% of the Indian population were affected by psoriasis in 2016-2017 [12]. Plaque, guttate, inverse, pustular, and erythrodermic are the five major types of psoriasis. Plaque psoriasis, also known as psoriasis vulgaris, is the most common form of the disease (about 90% of the cases) [3] which typically presents with red patches with white scales on top. Psoriasis vulgaris which commonly affects the areas includes scalp, knees, elbows, hands, nails, and feet [4].

Psoriasis, an autoimmune-inflammatory disease probably predisposed due to genetic makeup, is mediated by T-helper cells. Polymorphism, referred to as differences in DNA sequences of a gene, can be incurred by various external agents like chemicals, viruses, or radiation. Polymorphisms in genes of Th2 cytokine/regulatory T-cell (interleukin-10/IL10), Th1/Th17 cytokine (IL-12B and IL-23R), and tumour necrosis factor alpha (TNFAIP3; TNIP1) confer which increased other risks like cardiovascular diseases amongst psoriasis patients [57]. Single nucleotide alteration caused polymorphism in Th1 proinflammatory cytokine gene IL-2 [–330 (G/T)] which has been shown to be associated with greater disease severity in the Indian population [1]. On the other hand, another gene polymorphism occurring in Th-2 cytokine/regulatory T-cell (IL-4) has been shown to be protective against psoriasis [5]. Upregulation in the levels of inflammatory cytokines leads to psoriasis which also can be associated with an increased risk of psoriatic arthritis, lymphomas, cardiovascular risk, Crohn’s disease, and depression [3]. There is no permanent cure for psoriasis, though steroid creams, vitamin D3 cream, ultraviolet light, and immune system suppressing medications (methotrexate) have been in wide use to help control the symptoms with some success [89].

Mesenchymal stem cells (MSCs) are multipotent adult stem cells which have an excellent capacity to proliferate for an extended period of time while maintaining the undifferentiated cell status. The resulting daughter cells can differentiate into various types of cells of host tissues and thus help repair wear and tear incurred [10]. MSCs have a potential to serve as a powerful tool in cell-based therapy due to their tissue regenerative and host immune modulatory capabilities. The functions exhibited by MSCs have attracted a number of scientists and clinicians to investigate the mechanisms involved in their curative and tissue regeneration functions. A very few articles have reported the effectiveness of stromal vascular fraction (SVF)/MSC therapy in curing psoriasis by regulating the immune systems. Lee et al. [11] reported that human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) ameliorate psoriasis-like skin inflammation in mice and have regulatory effects on immune cells including CD4+ T cells and dendritic cells. The first case study on intravenous infusion of SVF into psoriasis patient demonstrated a significant decrease in symptoms with a noticeable difference in skin appearance, psoriasis area, and severity index (PASI) score reduction (from 50.4 to 0.3) [12]. Chen et al. [13] reported that umbilical cord-derived MSC (UC-MSC) infusion effectively reduced psoriasis in human subjects. It was believed that MSCs’ migration into the skin lesions and their immunomodulatory, autoimmune inhibitory, and paracrine effects were the principal factors behind the ameliorative effects. Other recent preclinical studies have shown that stem cell-derived conditioned media (CM) exhibit effective healing of psoriasis-like wounds and thus CM is an alternative for several cell-based therapies [1415]. The paracrine factors including growth factors, chemokines, and cytokines secreted from stem cells play a major role in wound healing [16] and these molecules are present in CM or spent medium harvested from cultured cells [17]. In short, CM can serve as a novel treatment approach in regenerative medicine which has been shown to have a successful outcome in preclinical studies. However, a very few reports are available on the clinical application of CM for treatment of any disease. Based on the principles and importance of CM, the present study was aimed at investigating the effect of MSC-CM on a patient suffering from psoriasis. This study is believed to be the first clinical report on the use of MSC-CM to treat psoriasis.

2. Case Report

2.1. Patient

A 38-year-old male patient, who was suffering from psoriasis vulgaris for 2 years, paid a visit to our centre. Preliminary examination of the patient showed that numerous erythematous plaques with numerous silvery scales present all over the scalp including the area behind the ears. The severity of the disease was assessed to be 28 on Psoriasis Scalp Severity Index (PSSI), calculated by the standard method which combines the severity (erythema, induration, and desquamation) and percentage of affected area.

2.2. Preparation of MSC-Conditioned Media

Adipose tissue was collected from a healthy volunteer by lipoaspiration by a plastic surgeon under the aseptic conditions in the O.T. About 100 ml of fat was aspirated out from the waist area and collected in a sterile container. The fat tissue contacting stem cells was processed in a biosafety laminar airflow chamber. MSCs were isolated from adipose tissue by standard enzymatic digestion method with 0.1% collagenase type I. Following the centrifugation, the resulting pellet was cultured in DMEM medium (Invitrogen, Paisley UK) supplemented with 10% foetal bovine serum (FBS) and 1% penicillin/streptomycin, at 37°C in humidified atmosphere containing 5% CO2. The media were changed after every 3 days. About 5×106 MSCs of passage 2 were seeded in each T175 culture flask (n=10) containing 30 ml of DMEM medium supplemented with 10% FBS. MSCs were confirmed with spindle shaped morphology and free from any contamination (Figure 1) using a phase-contrast microscope. When cells attained 90% confluence at passage 2, the culture media were replaced with serum-free DMEM. After 72 h of incubation, resulting MSC-CM was collected, centrifuged at 2000 rpm for 5 min to remove the cell debris, filtered through 0.22-μm filter, and then concentrated (10 times) by ultrafiltration using centrifugal filtering units with a cut-off value of 3 kDa (Amicon Ultra-15; Millipore, MA), according to the manufacturer’s instructions. The concentrated MSC-CM was aliquoted and stored at -20°C until use. MSC-CM was topically applied on the afflicted areas once a day over a period of one month. Clinical parameters like severity, changes, and clearance of psoriatic plaques were monitored at regular intervals.

Figure 1: Phase-contrast microscopic image showing spindle shaped MSCs (× 100).
2.3. MSC-CM Ameliorates Psoriasis Vulgaris

Numerous psoriatic erythematous plaques with adhering silvery scales over the different regions of the scalp were observed before the treatment regimen started. In general, the number of the scales declined significantly within 2 weeks of topical application of MSC-CM. Interestingly, clearance of silvery scales and severity of psoriatic plaques were completely abolished within one month of the treatment (Figure 2). The PSSI score reduced to 0 from 28 and regression of the disease continued for 6 months of follow-up. The patient did not take any other medication during the follow-up period of six months and led an improved quality of life without any adverse side effects.

Figure 2: Effect of MSC-CM on psoriasis vulgaris. The scalp of patient showing numerous erythematous plaques with adherent silvery flakes before MSC-CM-treatment (a, b). Regression of psoriasis and a complete clearance of inflammatory erythematous plaques recorded after topical application of MSC-CM for a period of one month (c, d).

3. Discussion

Psoriasis is an autoimmune disease mediated by hyperactivity of T-helper cells. Increases in the levels of inflammatory cytokines triggered by T cells lead to psoriasis and other associated diseases [3]. Therapies using multipotent MSCs have been shown to be effective in treating psoriasis and psoriasis-like other skin diseases. Clinical benefits may be attributed to MSCs engraftment or to their paracrine/immunomodulatory effects. However, transplanting MSCs come with few limitations like low survivability of cells in the host due to harsh microenvironment and cell loss because of poor or no cell adhesion [18]. Hence there is need of the hour to find an alternative for cell-based therapy.

Cell-free products of MSC origin are effective in wound healing and skin diseases. In this study, we demonstrated that MSC-CM can be used to treat patients with chronic psoriasis. Prior to MSC-CM treatment, the patient had received different medications but without any noticeable effective outcome. Remarkably, topical application of MSC-CM for a period of only one month completely abolished the erythematous plaques and resulted into a complete clearance of adherent silvery scales over the scalp. Further, the severity of psoriasis was completely reduced, from PSSI score of 28 to 0. This regeneration of tissue and improvement of qualitative appearance skin may be mediated by the growth factors, chemokines, and cytokines present in MSC-CM. Previous reports have shown that the paracrine factors secreted by MSC present in CM play a vital role in the healing of psoriasis-like wounds [1617]. Kim et al. [19] stated that adipose-derived stem cell (ADSC)-CM has regenerative effects on skin wounds. It stimulates both collagen synthesis, migration of dermal fibroblasts and promotes wound healing in animal models. ADSC-CM also upregulates the transcription of type I procollagen-alpha-1 chain gene of fibroblasts and induces Rho-associated kinase (RhoA-ROCK) signalling pathway, which leads to the proliferation of keratinocytes and dermal fibroblasts. In other studies [2021], MSC-CM promoted the recovery of skin burn wounds in rats, marked by an acceleration of wound closure, greater numbers of fibroblasts around and injured tissue and blood vessels, high epithelialization ratio, and high density of collagen fibres. It was suggested that basic fibroblast growth factor (bFGF) played an important role in the tissues regeneration of skin burn treated by MSC-CM.

In vitro and in vivo studies involving UC-MSC-CM demonstrated that its application caused an increase in the proliferation and migration of dermal fibroblasts, decrease in the ratio of transforming growth factor-β1/β3, and an increase in the ratio of matrix metalloproteinase over counter agent tissue inhibitor of metalloproteinases [22]. Similarly, human embryonic stem cell (hESC)-derived endothelial precursor cells CM is a rich source of a number of growth factors like epidermal growth factor (EGF), bFGF, fractalkine, granulocyte-macrophage colony-stimulating factor (GM-CSF), and interleukin (IL)-6. It was successfully used in the treatment of excisional wound healing in rats [23]. A comparative study revealed that wound healing by bone-marrow derived mesenchymal stem cell (BMMSC)-CM was significantly higher than that by fibroblast-CM [16]. The fact that BMMSC-CM had higher levels of paracrine factors than those in fibroblast-CM indicated the importance of origin of cells played a significant role in the production of paracrine factors. Other growth factors like Vascular endothelial growth factor (VEGF), insulin like growth factor (IGF), EGF, keratinocyte growth factor (KGF), angioprotein-1 (Ang-1), stromal derived factor-1, and erythropoietin (EPO) were also present in BMMSC-CM. With the supporting evidence of previous reports, the ameliorative effect of MSC-CM exhibited in this present study could be attributed to the presence of numerous growth factors secreted by MSCs in the media.

4. Conclusions

This is the first case report which demonstrates the ameliorative effect of MSC-CM on psoriasis vulgaris. MSC-CM is likely to have a wide range of cytokines and growth factors which can directly act on resident skin cells and thus can help in the skin regeneration. The active bioactive ingredients and their needed combination are yet to be determined. Use of MSC-CM instead of direct implantation of MSCs to tackle the issue offers an alternative approach which overcomes a number of limitations of cell-based therapy. In conclusion, treatment using MSC-CM appears to be highly effective for the treatment of psoriasis and may represent a new avenue of therapy. Further investigations for addressing a number of question provoked by the findings reported here, such as long-term effects (over a period of years), induced changes at cellular and histological levels, and identification of involved bioactive molecules, demand more studies.

Ethical Approval

This study was approved by the Institutional Ethics Committee (approval no. ECR/303/Indt./GJ/2018).

Consent

The patient and the volunteer, participating in the study, were informed about the procedures and their consent was obtained in advance.

Conflicts of Interest

The authors declare that they have no conflicts of interest.

References

  1. D. M. Thappa and M. Munisamy, “Research on psoriasis in India: Where do we stand?” Indian Journal of Medical Research, vol. 146, no. 2, pp. 147–149, 2017. View at Publisher · View at Google Scholar · View at Scopus
  2. WHO, Global Report on Psoriasis, 2016.
  3. W. H. Boehncke and M. P. Schon, “Psoriasos,” Lancet, vol. 386, pp. 983–994, 2015. View at Google Scholar
  4. C. G. Helmick, H. Lee-Han, S. C. Hirsch, T. L. Baird, and C. L. Bartlett, “Prevalence of psoriasis among adults in the U.S.: 2003-2006 and 2009-2010 national health and nutrition examination surveys,” American Journal of Preventive Medicine, vol. 47, no. 1, pp. 37–45, 2014. View at Publisher · View at Google Scholar · View at Scopus
  5. S. Indhumathi, M. Rajappa, L. Chandrashekar, P. H. Ananthanarayanan, D. M. Thappa, and V. S. Negi, “TNFAIP3 and TNIP1 polymorphisms confer psoriasis risk in South Indian Tamils,” British Journal of Biomedical Science, vol. 72, no. 4, pp. 168–173, 2015. View at Publisher · View at Google Scholar · View at Scopus
  6. S. Indhumathi, M. Rajappa, L. Chandrashekar, P. H. Ananthanarayanan, D. M. Thappa, and V. S. Negi, “Investigation of association of the IL-12B and IL-23R genetic variations with psoriatic risk in a South Indian Tamil cohort,” Human Immunology, vol. 77, no. 1, pp. 54–62, 2016. View at Publisher · View at Google Scholar · View at Scopus
  7. S. Indhumathi, M. Rajappa, L. Chandrashekar, P. H. Ananthanarayanan, D. M. Thappa, and V. S. Negi, “T helper-2 cytokine/regulatory T-cell gene polymorphisms and their relation with risk of psoriasis in a South Indian Tamil cohort,” Human Immunology, vol. 78, no. 2, pp. 209–215, 2017. View at Publisher ·View at Google Scholar · View at Scopus
  8. A. Menter and C. E. Griffiths, “Current and future management of psoriasis,” The Lancet, vol. 370, no. 9583, pp. 272–284, 2007. View at Publisher · View at Google Scholar · View at Scopus
  9. A. Menter, A. Gottlieb, S. R. Feldman et al., “Guidelines of care for the management of psoriasis and psoriatic arthritis. Section 1. Overview of psoriasis and guidelines of care for the treatment of psoriasis with biologics,” Journal of the American Academy of Dermatology, vol. 58, no. 5, pp. 826–850, 2008. View at Publisher · View at Google Scholar · View at Scopus
  10. R. S. Mahla, “Stem cells applications in regenerative medicine and disease therapeutics,” International Journal of Cell Biology, vol. 2016, Article ID 6940283, 24 pages, 2016. View at Publisher · View at Google Scholar
  11. Y. S. Lee, S. K. Sah, J. H. Lee, K.-W. Seo, K.-S. Kang, and T.-Y. Kim, “Human umbilical cord blood-derived mesenchymal stem cells ameliorate psoriasis-like skin inflammation in mice,” Biochemistry and Biophysics Reports, vol. 9, pp. 281–288, 2017. View at Publisher · View at Google Scholar · View at Scopus
  12. K. Comella, M. Parlo, R. Daly, and K. Dominessy, “First-in-man intravenous implantation of stromal vascular fraction in psoriasis: A case study,” International Medical Case Reports Journal, vol. 11, pp. 59–64, 2018. View at Publisher · View at Google Scholar · View at Scopus
  13. H. Chen, J. Niu, H. Ning et al., “Treatment of psoriasis with mesenchymal stem cells,” American Journal of Medicine, vol. 129, no. 3, pp. e13–e14, 2016. View at Publisher · View at Google Scholar
  14. J. A. Pawitan, “Prospect of stem cell conditioned medium in regenerative medicine,” BioMed Research International, vol. 2014, Article ID 965849, 14 pages, 2014. View at Google Scholar · View at Scopus
  15. M. N. M. Walter, K. T. Wright, H. R. Fuller, S. MacNeil, and W. E. B. Johnson, “Mesenchymal stem cell-conditioned medium accelerates skin wound healing: an in vitro study of fibroblast and keratinocyte scratch assays,” Experimental Cell Research, vol. 316, no. 7, pp. 1271–1281, 2010. View at Publisher · View at Google Scholar · View at Scopus
  16. L. Chen, E. E. Tredget, P. Y. G. Wu, Y. Wu, and Y. Wu, “Paracrine factors of mesenchymal stem cells recruit macrophages and endothelial lineage cells and enhance wound healing,” Plos One, vol. 3, no. 4, Article ID e1886, 2008. View at Publisher · View at Google Scholar · View at Scopus
  17. R. Shohara, A. Yamamoto, and S. Takikawa, “Mesenchymal stromal cells of human umbilical cord Wharton’s jelly accelerate wound healing by paracrine mechanisms,” Cytotherapy, vol. 14, no. 10, pp. 1171–1181, 2012. View at Publisher · View at Google Scholar · View at Scopus
  18. S. Lee, E. Choi, M. J. Cha, and K. C. Hwang, “Cell adhesion and long-term survival of transplanted mesenchymal stem cells: a prerequisite for cell therapy,” Oxidative Medicine and Cellular Longevity, vol. 2015, Article ID 632902, 9 pages, 2015. View at Publisher · View at Google Scholar
  19. W.-S. Kim, B.-S. Park, and J.-H. Sung, “Protective role of adipose-derived stem cells and their soluble factors in photoaging,” Archives of Dermatological Research, vol. 301, no. 5, pp. 329–336, 2009. View at Publisher · View at Google Scholar · View at Scopus
  20. I. Padeta, W. S. Nugroho, D. L. Kusindarta, Y. H. Fibrianto, and T. Budipitojo, “Mesenchymal stem cell-conditioned medium promote therecovery of skin burn wound,” Asian Journal of Animal and Veterinary Advances, vol. 12, no. 3, pp. 132–141, 2017. View at Publisher · View at Google Scholar
  21. T. Tarcisia, L. Damayanti, R. D. Antarianto, Y. Moenadjat, and J. A. Pawitan, “Adipose derived stem cell conditioned medium effect on proliferation phase of wound healing in sprague dawley rat,” Medical Journal of Indonesia, vol. 26, no. 4, pp. 239–245, 2017. View at Google Scholar · View at Scopus
  22. M. Li, F. Luan, Y. Zhao et al., “Mesenchymal stem cell-conditioned medium accelerates wound healing with fewer scars,” International Wound Journal, vol. 14, no. 1, pp. 64–73, 2017. View at Publisher · View at Google Scholar · View at Scopus
  23. M. J. Lee, J. Kim, K. I. Lee, J. M. Shin, J. I. Chae, and H. M. Chung, “Enhancement of wound healing by secretory factors of endothelial precursor cells derived from human embryonic stem cells,” Cytotherapy, vol. 13, no. 2, pp. 165–178, 2011. View at Publisher · View at Google Scholar · View at Scopus

Dr. Anand’s Editorial on Diabetes Type 1 & 2 in Journal of Stem Cell Research & Therapeutics

Dear Dr. Anand S Srivastava,

 

Congratulations!

We are very pleased to inform you that your manuscript has successfully gone through all the required processes for publication. Certainly, your article deserves its place on the JSRT’s bookshelf, and we will do our best to share your endeavors with the world. That’s a promise.

Moreover I would like to have your profile in our journal, so I request you to send us your CV at the earliest possibility.

Await your contribution.

Best regards,

Grace Victoria

Diabetes Type 1 & 2 in Journal of Stem Cell Research & Therapeutics

 Diabetes: Stem Cells Offering Healthy Promises

 

Aditi Saraswat,1 Anand Srivastava2
1Henry Ford Medical Center, USA
2Global Institute of Stem Cell Therapy and Research, USA
Received: April 30, 2018 | Published: May 09, 2018

Correspondence: Anand Srivastava, Global Institute of Stem Cell Therapy and Research, 4660 La Jolla Village Drive, San Diego, CA, 92122, USA, Tel 8583 4424 92, Email 

Citation: Saraswat A, Srivastava A. Diabetes: stem cells offering healthy promises. J Stem Cell Res Ther. 2018;4(2):45‒46. DOI:10.15406/jsrt.2018.04.00113

 

Editorial

Diabetes is a chronic lifelong disease and according to Diabetes Association of America, in 2015 itself approximately 30.3million Americans (9.4% of the population) have the disease. Unfortunately, almost one fourth (or approximately 7.2million) are unaware that they have it. An additional 84.1million people have pre-diabetes. With increasing prosperity, its prevalence has increased in almost all populations of the world and ranges from 5-15%. As it affects so big portion of the world population a long-lasting cure is urgently warranted. People with diabetes need to manage their disease in order to avoid related complications and maintain healthy social and economic interactions.

Diabetes affects individuals of all age groups and has been classified in two types. Type 1 diabetes (T1D) is an autoimmune disease that occurs when a person’s pancreas stops producing insulin. It is usually diagnosed in children and young adults, previously known as juvenile diabetes. Only 5% of people with diabetes have this form of the disease. On the other hand, type 2 diabetes (T2D) is the most common form of diabetes. In patients of T2D, the body does not use insulin properly mostly because of insulin resistance. Because of that, at first, pancreas compensates by making extra insulin. However, over time it isn’t able to keep up and can’t make enough insulin to keep your blood glucose at normal levels.

Diabetes affects every part of the body and causes complications related to heart, brain, kidney, circulatory system etc. Managing diabetes exerts a significant burden on the economy in general. During 2017, according to an estimate, diabetes-related care of people directly or indirectly could have costed around $327 billion.1 Though a number of medications are already in clinical use but none of them grant a long-term cure and all of them have some or other undesired side-effects.

 Since almost all pharmacological drugs, irrespective of the target molecule in the pathway involved in the manifestation of diabetes-related complications, have some side effects a safer and comparatively long last therapeutic alternative is desperately needed. To meet the continuous need for insulin, pancreatic transplants have been tried which turned out to be very cost-intensive and impractical because the donor pancreases have to be recovered from suitable cadavers and then transplanted.2 Logically, transplantation of a tissue from other individual comes up with so many concerns like compatibility of a graft in the new host and its survival as immune rejection is usually a valid concern most of the time. To circumvent all these concerns another alternative way of handling the problem was needed for a long time. Discovery of stem cells and related extensive research has offered a ray of hope to manage the problem efficiently with a sound possibility of a permanent cure.

Stem cells, depending on the source of their origin, are classified as embryonic or adult or induced. Embryonic stem cells are capable of differentiating in all cell types for a body while adult cells which have attained some tissue-specific differentiation, lose that ability slightly. Since a number of ethical issues crop up with use of embryonic cells, adult stem cells are next best type of cells to lean back on. Another favorable factor for using adult stem cells is that these can be isolated from tissues which are easy to extract from an individual like belly fat or bone marrow. Cells of these origins are classified as mesenchymal stem cells (MSCs). MSCs are known to promote the regeneration of pancreatic islet beta cells, protect endogenous pancreatic islet beta cells from apoptosis, and ameliorate insulin resistance of peripheral tissues by providing a supportive niche microenvironment driven by the secretion of paracrine factors or the deposition of extracellular matrix.3,4

In general, implantation of MSCs can alleviate T2D by a number of mechanisms. These cells, if implanted directly in the pancreas, thanks to their multipotential ability to differentiate in diverse types of cells of their immediate vicinity, can produce new insulin-producing cells. Investigators, in order to promote the chance of differentiation of cells in insulin-producing cells, have preprogrammed MSCs by culturing in serum-free high glucose media or neuron conditioned media before transplantation. Intravenous infusion of stem cell has been shown to regenerate beta cells of islets in rats5 also promote the survival during hypoxia and oxidant stress.6 In addition to these effects, infusion of stem cells has been shown to promote insulin sensitivity.7 Though the exact mechanism by which stem cell bring about increased insulin sensitivity is not deciphered, it could be because of stem-cell-mediated decrease in systemic inflammation as it is well established that insulin resistance is strongly correlated with chronic low-grade inflammation.

Encouraging findings in cases of diabetes treatments with stem cell therapies have led the clinicians to try implantation or infusion or both in the clinical set up also. On the clinical trial site of NIH, more than 150 trials at different stage have been listed. MSCs of diverse origins either were implanted directly in the pancreas8 or were infused in blood stream9 or both10 showed promising results up to 12 months of follow up. A couple of clinical parameters are often used to ascertain the effectiveness of a therapy in cases of diabetes. A decrease in Hb A1C is one of those parameters which were used by Estrada et al.11 and they reported a significant decrease.11 In another study, insulin need decreased or was abolished altogether.8 Similarly, implantation or infusion of MSCs has been shown to improve pancreatic function i.e. increased insulin production. Same time, increased insulin sensitivity is also attained by MSCs.

Just like other medical helps, stem cell therapy can have some undesirable effects, though the incidences are few and far between. Even those undesired effects, which happen after stem cell transplantation are very mild and easily manageable like mild to moderate fever or nausea or headache.

In conclusion, stem cell therapy does offer a long lasting therapeutic alternative for treating T2D. Same time it has to be kept in minds of both clinicians and patients that it is not a permanent cure. T2D is a metabolic syndrome which manifests after a long duration of unhealthy life style which needs to be addressed in order to lead a healthy life. Compared to all other available therapies, stem cell therapy can offer a lot longer period for individuals to develop a healthy life style which would help fend off re-occurrence of the disease.

Conflict of interest

 

Author declares that there is no conflict of interest.

References

 

  1. Enocrinology Advisor. Total Estimated Cost of Diagnosed Diabetes $327 Billion in 2017. Endocrinology Advisor. 2017.
  2. Shapiro AM, Lakey JR, Ryan EA, et al. Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen. N Engl J Med. 2000;343(4):230‒238.
  3. Caplan AI, Dennis JE. Mesenchymal stem cells as trophic mediators. J Cell Biochem. 2006;98(5):1076‒1084.
  4. Lee RH, Seo MJ, Reger RL, et al. Multipotent stromal cells from human marrow home to and promote repair of pancreatic islets and renal glomeruli in diabetic NOD/scid mice. Proc Natl Acad Sci U S A. 2006;103(46):17438‒17443.
  5. Hao H, Liu J, Shen J, et al. Multiple intravenous infusions of bone marrow mesenchymal stem cells reverse hyperglycemia in experimental type 2 diabetes rats. Biochem Biophys Res Commun. 2013;436(3):418‒423.
  6. Chandravanshi B, Bhonde RR. Shielding Engineered Islets With Mesenchymal Stem Cells Enhance Survival Under Hypoxia. J Cell Biochem. 2017;118(9):2672‒2683.
  7. Hughey CC, Ma L, James FD, et al. Mesenchymal stem cell transplantation for the infarcted heart: therapeutic potential for insulin resistance beyond the heart. Cardiovasc Diabetol. 2013;12:128.
  8. Bhansali A, Asokumar P, Walia R, et al. Efficacy and safety of autologous bone marrow-derived stem cell transplantation in patients with type 2 diabetes mellitus: a randomized placebo-controlled study. Cell Transplant. 2014;23(9):1075‒1085.
  9. Jiang R, Han Z, Zhuo G, et al. Transplantation of placenta-derived mesenchymal stem cells in type 2 diabetes: a pilot study. Front Med. 2011;5(1):94‒100.
  10. Liu X, Zheng P, Wang X, et al. A preliminary evaluation of efficacy and safety of Wharton’s jelly mesenchymal stem cell transplantation in patients with type 2 diabetes mellitus. Stem Cell Res Ther. 2014;5(2):57.
  11. Estrada EJ, Valacchi F, Nicora E, et al. Combined treatment of intrapancreatic autologous bone marrow stem cells and hyperbaric oxygen in type 2 diabetes mellitus. Cell Transplant. 2008;17(12):1295‒1304.

 

 

Role of Cell Based Approaches in Cancer Immunotherapy

 

Anjum Mahmood,1 Anjani Srivastava,2 Shivangi Srivastava,2Hiteshree Pandya,1 Neel Khokhani,1 Divyang Patel,1 Rangnath Mishra3
1GIOSTAR Research Pvt Ltd, India
2Global Institute of Stem Cell Therapy and Research, USA
3Department of Medicine, National Jewish Health, USA
Received: February 17, 2017 | Published: May 05, 2017

Correspondence: Rangnath Mishra, Department of Medicine, National Jewish Health, Denver, CO 80206, USA, Email

Citation: Mahmood A, Srivastava A, Srivastava S, et al. Role of cell based approaches in cancer immunotherapy. J Stem Cell Res Ther. 2017;2(5):145‒147. DOI: 10.15406/jsrt.2017.02.00077

Abstrat

Immunotherapies hold the potential for cancer treatment since their mode of action is distinct to chemo and radiation therapy and largely depends on harnessing body’s own immune system. The major advantage associated with cancer immunotherapy is that cell responses are specific to tumor and with low or negligible toxicity. Preclinical and clinical studies have evidenced that modulation of immune system can subvert the immunosuppressive environment under progressive tumor conditions. The modulation can be brought into several ways including infusion of ex-vivo or in-vivo activated antigen presenting cells (dendritic cells), immune checkpoint antibodies, adoptive transfer of T cells, genetically modified T cells, cancer cell vaccines, stem cells, cytokines and others. In this review, we will keep the discussion focused to some of cell based approaches.

Keywords: immunotherapy, dendritic cells, adoptive t cell therapy, mesenchymal stem cells, cancer

Abbreviations

DCs, dendritic cells; MSCs, mesenchymal stem cells; MDSCs, myeloid derived suppressor cells; BBB, blood brain barrier; CAR, chimeric antigen receptor, IFN, interferon; TILs, tumor infiltrating lymphocytes; CSCs, cancer stem cells; PBMCs, peripheral blood mononuclear cells; IL, interleukin

Introduction

An integrated immune system prevents development and progression of neoplastic cells in a process termed as immune surveillance. T-cells play an important role in detecting and eliminating tumor cells. In turn, they are dependent on dendritic cells for tumor antigen presentation and activation signals to stimulate them. One of the most important reasons behind failure of cancer immuno-surveillance is hampered T-cell activity due to lack of co-stimulatory activation signals by dendritic cells resulting into peripheral tolerance. Other factors driving tumor progression include immunosuppressive tumor micro-environment, infiltration of regulatory T cells, release of immunosuppressive cytokines like IL-10 and TGF-β, reduced expression of MHC molecules, myeloid derived suppressor cells (MDSCs) and heterogeneity of tumor sub-clones at the genetic level. Studies have shown that expansion of Treg cells is associated with poor prognosis and reduced survival. Similarly, abnormal accumulation of MDSCs is also correlated with tumor evasion mechanism. Though, chemotherapy is first line of treatment, the efficacy is restricted later due to development of drug resistance. The major reasons for resistance development includes drug-targeted gene amplification (e.g. BRAF gene) and substitution mutation in some cancer cells leading to the escape of drug cytotoxic effect.1Further, non-specific cytotoxicity of chemo agents result into lymphodepliton. To address all these issues, new therapeutic interventions are required which alone or in combination alter the tumor microenvironment to enhance beneficial effects without causing toxicity. In this context, immunotherapy is expected to play significant role. Cancer immunotherapy can be defined as set of techniques aimed to eliminate malignant tumors through mechanisms involving immune system responses. The agents driving immune alteration are termed as immunomodulators. In this review, we will discuss briefly some of specific methods mediating immunomodulation including dendritic cell based approaches, adoptive T cells transfer and mesenchymal stem cells based targeted delivery of drugs.

Dendritic cells

The dendritic cells (DCs) based immunotherapeutic approach has emerged as one of alternative treatment options owing to its low toxicity in comparison to other standard methods. The clinical efficacy has been demonstrated with improvement in overall survival rate and low toxicity. The application of ex-vivo-generated DCs emerged in an effort to improve the therapeutic efficacy in cancer patients in whom the dysfunction of endogenous DCs is commonly observed. The DCs are generated using several approaches. The most common used method is ex-vivo differentiation of DCs from peripheral blood mononuclear cells (PBMCs) using interleukin-4 (IL-4) and granulocyte macrophage colony stimulating factor (GM-CSF).2 Other ways of generating ex-vivo DCs is to derive it from progenitor CD34+ cells or in-vivo stimulation using C-type lectin receptors (CLRs) present on DC surfaces. CLRs specific antibodies attached to tumor antigens are readily internalized by DCs and generate antigen specific antitumor immunity.3,4

In terms of clinical success, initially most of phase I/II studies demonstrated only safety and feasibility. The efficacy remained an issue in phase III due to inconsistent and inconclusive data. The first successful commercialized product was Sipuleucel-T for castration resistant prostate cancer. The vaccine was approved by FDA in 2010.5 The approval was based on phase III results of IMPACT (Immunotherapy Prostate Adenocarcinoma Treatment) trials. Later, several other studies demonstrated beneficial effect of DC immunotherapy in head and neck squaous cell carcinoma,6 uterus,7 prostate8and breast cancer and Her-2 positive ductal carcinoma in-situ.9 However, for most cancers, preclinical success could not be translated up to phase III due inconstant data and less optimized process.

Adoptive t cell therapy

Adoptive transfer of T cells is a potent treatment option for metastatic tumors. The T cell based interventions are specific, robust (undergoing upto 1000 fold clonal expansion) and retain memory. Further, T cells can infiltrate to the site of antigen and thus holds capacity to eradicate distant metastasis. In chimeric antigen receptor (CAR) approach T cells are engineered cells which provide specificity to the effector cells. Most of clinical investigations targeted B cell related malignancies using CD19 directed CART cells. These studies demonstrated response in many patients.10–12 Antigens like human epidermal growth factor receptor over-expressed in tumors like breast, ovarian, non small cell lung carcinoma (NSCLC), salivary gland, pancreatic and endometrial cancers are under investigation for CART cell development.13–17 Till now, most of the success of CART cells is limited around hematological malignancies, a huge scope is still available for exploring new antigens, directed to eliminate metastatic, resistant and non-hematological malignancies.

Tumor infiltrating lymphocytes (TILs) are found in the tumor region and are associated with anti-tumor activity. They are isolated from tumor, expanded under ex-vivo conditions, screened for anti-neoplastic activity and infused back into patients. Their presence in tumor is associated with better clinical outcome. These lymphocytes at tumor site recognize the antigens presented by MHCI and MHC II molecules on cell surfaces. TILs raised against melanoma recognize antigens especially MART-1, gp100 and tyrosinase.18–21 Another class of antigens termed as cancer/testis (C/T) antigens are also recognized by melanoma TILs. The class includes several antigens like MAGE, NYESO-1, RAGE, SAGE and SSX2.22,23 Rosenberg et al was pioneer in isolation and expansion of melanoma specific TILs developed for clinical purposes.24 Rosenberg et al.,24 conducted three sequential clinical trials, in which 93 patients (metastatic melanoma) were treated with lympho depleting preparative regimen, autologous TILs and IL2. Objective response rates by RECIST criteria in the three trials were 49%, 52% and 72%, respectively. Study showed that 22% of all patients achieved complete tumor regression and 19% of the patients were disease-free for more than three years.25 Till now, most of the clinical investigations focused on melanoma due to considerable success. However, non melanoma tumors demonstrated less feasibility due to lack of reproducibility of TIL generation from primary and metastatic tumors.

Mesenchymal stem cells

Mesenchymal stem cells (MSCs) are adult stem cells with unique characteristic ability of homing, facilitating their application in cancer immunotherapy. These adult stem cells are reported to migrate at site of inflammation, injury, infection and tumors where they immunomodulate the immediate micro-environment through secretion of soluble factors.26 The therapeutic value to MSCs is conferred by transportation of anti-tumor genes. MSCs act as delivery vehicle for many tumor inhibiting genes and factors to tumor site.27 They offer therapeutic advantage of ease of isolation, ex-vivo expansion, transduction and transplantation. The movement of MSCs to tumor site is driven by chemotactic factors, chemokines and chemo-attractants released by progressive tumors.28 MSCs hold another characteristic feature which makes them a favorable tool for carrying targeted anti-cancer gene i.e., they are immunoprivileged. The absence or low expression of MHC II, MHC I, CD80, CD40, and CD86 molecules on cell surface make them undetectable by host immune system. Further, immunoprivileged nature also confers possible use of allogenic MSCs. However, at same time, MSCs are immunosuppressive, which exerts significant effect on host disease. In case of graft versus host disease, transplant of MSCs offer a promising treatment, where disease can develop due to histo-compatibility mismatch.29 On other hand, application of MSCs can induce tumor progression due to immune inhibition.

Several genes demonstrating therapeutic efficacy in preclinical models have been tested for expression in MSCs as vehicle. The genes which have been engineered in MSCs to target tumor sites include IL-12, VEGFR-1, CX3CL1, HSV-Tk, TRAIL and IFNβ.30–33 Their expressions were related to localized and metastatic tumor inhibition and survival benefits in tumor models. HSV-Tk (herpes simplex virus thymidine kinase) is a pro drug converting enzyme which is delivered through MSCs along with systemic administration of ganciclovir. In this approach, which has been successfully tested in glioma and pancreatic cancer, MSCs carry the suicide enzymes to the tumor site thus avoiding systemic toxicity.34 In brain tumors like glioma where blood brain barrier (BBB) restrict passage of anti tumor therapy, MSCs based delivery of drugs can provide therapeutic solutions.35

Future directions

Recent advances in understanding the mechanism underlying tumor progression and role of immune system has laid the foundation of immunotherapy based interventions in clinical malignancies. By adopting unique immunotherapeutic approach specific to diseased condition and optimal conditions of delivery significant level of benefits can be expected. Further, exploration of new targeted strategies is also required to extend scope of application and avoid unwanted adverse events in patients. The targeting of other identified DC cell surface receptors like mannose receptor (MR), CIRE, DC-SIGN, DCIR, LSECtin, L-SIGN, Langerin, Dectin, DNGR-1, MICL, MGL CLEC2, CLEC12B, LOX-1, BDCA-2, DEC205, scavenger receptor, DC-ASGPR, FIRE, DC-STAMP and Toll-like receptors (TLRs) will definitely open the new dimensions in in-vivo DC based approaches.5 Further, targeting of cancer stem cells (CSCs) via DCs will also improve specificity of anti-tumor activity. Similarly, role of MSC derived exosomes in delivery of therapeutic agents is also currently under investigation in several studies. Exosome-mediated delivery of tumor suppressor miRNAs and targeting of growth-regulatory pathways, such as the Wnt and Hedgehog pathways, as well as angiogenic pathways, such as the VEGF and kinase pathways, could be novel strategies to monitor tumor growth. In light of current knowledge and advances in cancer immunotherapy we conclude that under optimal conditions, tangible benefits can be realized in cancer management.

Acknowledgements

None.

Conflict of interest

The author declares no conflict of interest.

References

  1. Mahmood A, Rajasekar S, Bora C, et al. Synergistic Effect of dendritic cell vaccine with immune modulating chemo drugs. Journal of Academia and Industrial Research. 2015;3(12):590–597.
  2. O’Neill DW, Bhardwaj N. Differentiation of peripheral blood monocytes into dendritic cells. Curr Protoc Immunol. 2005;Chapter 22:Unit 22F, 4.
  3. Banchereau J, Palucka AK, Dhodapkar M, et al. Immune and clinical responses in patients with metastatic melanoma to CD34+ progenitor–derived dendritic cell vaccine. Cancer Res. 2001;61(17):6451–6458.
  4. Turnis ME, Rooney CM. Enhancement of dendritic cells as vaccines for cancer. Immunotherapy. 2010;2(6):847–862.
  5. Higano CS, Schellhammer PF, Small EJ, et al. Integrated data from 2 randomized, double–blind, placebo–controlled, phase 3 trials of active cellular immunotherapy with sipuleucel–T in advanced prostate cancer. Cancer. 2009;115(16):3670–3679.
  6. Schuler PJ, Harasymczuk M, Visus C, et al. Phase I dendritic cell p53 peptide vaccine for head and neck cancer. Clin Cancer Res. 2014;20(9):2433–2444.
  7. Coosemans A, Vanderstraeten A, Tuyaerts S, et al. Wilms’ Tumor Gene 1 (WT1)–loaded dendritic cell imunotherapy in patients with uterine tumors:a phase I/II clinical trial. Anticancer Res. 2013;33(12):5495–5500.
  8. Hildenbrand B, Sauer B, Kalis O, et al. Immunotherapy of patients with hormone–refractory prostate carcinoma pre–treated with interferon–gamma and vaccinated with autologous PSA–peptide loaded dendritic cells–a pilot study. Prostate. 2007;67(5):500–508.
  9. Sharma A, Koldovsky U, Xu S, et al. HER–2 pulsed dendritic cell vaccine can eliminate HER–2 expression and impact ductal carcinoma in situCancer. 2012;118(17):4354–4362.
  10. Lee D, Kochenderfer J, Stetler–Stevenson M, et al. T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 dose–escalation trial. Lancet. 2014;385(9967):517–528.
  11. Gardner R, Jensen M. CD19CAR T cells: from humble beginnings to cancer immunotherapy’s poster child. Cancer J. 2014;20:107–111.
  12. Tasian SK, Gardner RA. CD19–redirected chimeric antigen receptor–modified T cells: a promising immunotherapy for children and adults with B–cell acute lymphoblastic leukemia (ALL). Ther Adv Hematol. 2015;6(5):228–241.
  13. Whilding LM, Maher J. ErbB–targeted CAR T–cell immunotherapy of cancer.Immunotherapy. 2015;7(3):229–241.
  14. Scholl S, Beuzeboc P, Pouillart P. Targeting HER2 in other tumor types. Annals of Oncology. 2001;12(Suppl 1):S81–S87
  15. Ahmed N, Brawley VS, Hegde M, et al. Human epidermal growth factor receptor 2 (HER2)–specific chimeric antigen receptor–modified T cells for the immunotherapy of HER2–positive sarcoma. J Clin Oncol. 2015;33(15):1688–1696.
  16. Feng K, Guo Y, Dai H, et al. Chimeric antigen receptor–modified T cells for the immunotherapy of patients with EGFR–expressing advanced relapsed/refractory non–small cell lung cancer. Science China Life Sciences. 2016;59(5):468–479.
  17. Almåsbak H, Aarvak T, Vemuri MC. CAR T cell therapy: A game changer in cancer treatment. Journal of Immunology Research. 2016;2016:10.
  18. Bakker AB, Schreurs MW, de Boer AJ, et al. Melanocyte lineage–specific antigen gp100 is recognized by melanoma–derived tumor–infiltrating lymphocytes. J Exp Med. 1994;179(3):1005–1009.
  19. Engelhard VH, Bullock TN, Colella TA, et al. Antigens derived from melanocyte differentiation proteins:self–tolerance, autoimmunity, and use for cancer immunotherapy. Immunol Rev. 2002;188:136–146.
  20. Robbins PE, el–Gamil M, Kawakami Y, et al. Recognition of tyrosinase by tumor–infiltrating lymphocytes from a patient responding to immunotherapy. Cancer Res. 1994;54(12):3124–3126.
  21. Romero P, Gervois N, Schneider J, et al. Cytolytic T lymphocyte recognition of the immunodominant HLA–A*0201–restricted Melan–A/MART–1 antigenic peptide in melanoma. J Immunol. 1997;159(5):2366–2374.
  22. Chen YT, Gure AO, Tsang S, et al. Identification of multiple cancer/testis antigens by allogeneic antibody screening of a melanoma cell line library. Proc Natl Acad Sci USA. 1998;95(12):6919–6923.
  23. Scanlan MJ, Gure AO, Jungbluth AA, et al. Cancer/testis antigens: an expanding family of targets for cancer immunotherapy. Immunolog Rev. 2002;188:22–32.
  24. Rosenberg SA, Packard BS, Aebersold PM, et al. Use of Tumor–Infiltrating Lymphocytes and Interleukin–2 in the Immunotherapy of Patients with Metastatic Melanoma. N Engl J Med. 1988;319(25):1676–1680.
  25. Rosenberg, SA, Yang JC, Sherry RM, et al. Durable complete responses in heavily pretreated patients with metastatic melanoma using T cell transfer immunotherapy. Clin Cancer Res. 2011;17(13):4550–4557.
  26. Gotherstrom C. Immuno– modulation by multipotent mesenchymal stromalcells. Transplantation. 2007;84(1 Suppl):S35–S37.
  27. Loebinger MR, Janes SM. Stem cells as vectors for antitumour therapy. Thorax. 2010;65(4):362–369.
  28. Menon LG, Picinich S, Koneru R, et al. Differential gene expression associated with migration of mesenchymal stem cells to conditioned medium from tumor cells or bone marrow cells. Stem Cells. 2007;25:520–528.
  29. Ringden O, Uzunel M, Rasmusson I, et al. Mesenchymal stemcells for treatment of therapy–resistant graft– versus–host disease. Transplantation. 2006;81(10):1390–1397.
  30. Studeny M, Marini FC, Champlin RE, et al. Bone marrow–derived mesenchymal stem cells as vehicles for interferon–beta delivery into tumors. Cancer Res. 2002;62(13):3603–3608.
  31. Sasportas LS, Kasmieh R, Wakimoto H, et al. Assessment of therapeutic efficacy and fate of engineered human mesenchymal stem cells for cancer therapy. Proc Natl Acad Sci USA. 2009;106(12) 4822–4827.
  32. Eliopoulos N, Francois M, Boivin MN, et al. Neo–organoid of marrow mesenchymal stromal cells secreting interleukin–12 for breast cancer therapy. Cancer Res. 2008;68(12):4810–4818.
  33. Xin H, Sun R, Kanehira M, et al. Intratracheal delivery of CX3CL1–expressing mesenchymal stem cells to multiple lung tumors. Mol Med. 2009;15(9–10):321–327.
  34. Uchibori R, Okada T, Ito T, et al. Retroviral vector–producing mesenchymal stem cells for targeted suicide cancer gene therapy. J Gene Med. 2009;11(5):373–381.
  35. Gu C, Li S, Tokuyama T, et al. Therapeutic effect of genetically engineered mesenchymal stem cells in rat experimental leptomeningeal glioma model. Cancer Lett. 2010;291(2):256–262.

A research team at Sahlgrenska Academy in Sweden has managed to create cartilage tissue from stem cells using a 3D printer. The fact that stem cells survived the printing is seen as a major success in itself and could potentially serve as an important step in the quest to 3D-print body parts.

The research, which took three years to complete, was carried out in collaboration with the Chalmers University of Technology, which is recognized for its expertise in 3D-printing biological materials, as well as researchers of orthopedics at Kungsbacka Hospital, a joint statement said.

The research team used cartilage cells taken from humans in connection with knee surgery. Subsequently, the cells were reversed in their development under lab conditions to become so-called pluripotent stem cells, which are cells that have the potential to develop into any kind of cells. Later, they were enclosed in a structure of nanocellulose using a 3D printer. After printing, the cells were treated with growth factors to form cartilage.

The research, which took three years to complete, was carried out in collaboration with the Chalmers University of Technology, which is recognized for its expertise in 3D-printing biological materials, as well as researchers of orthopedics at Kungsbacka Hospital, a joint statement said.

The research team used cartilage cells taken from humans in connection with knee surgery. Subsequently, the cells were reversed in their development under lab conditions to become so-called pluripotent stem cells, which are cells that have the potential to develop into any kind of cells. Later, they were enclosed in a structure of nanocellulose using a 3D printer. After printing, the cells were treated with growth factors to form cartilage.

“The differentiation of stem cells into cartilage works easily in nature, but is significantly more difficult to perform in test tubes. We are the first to succeed in it,” associate professor of cell biology Stina Simonsson said, as quoted by the Swedish newspaper Hällekis Kuriren, venturing that the key to succeeding was tricking the cells into “believing” they were not alone.

Earlier this year, human cartilage cells were successfully implanted in six-week-old baby mice. Once implanted, the tissue began to grow and proliferate inside the animal, eventually vascularizing and growing with blood vessels.

The end product, which was developed using a Cellink 3D bio-printer, was found to be very similar to human cartilage. Experienced surgeons argued that printed cartilage looked “no different” from that found in patients.

On top of being a major technological achievement, the study represents a major step forward for the artificial creation of human tissue. In the not-too-distant future, 3D printers could be used for repairing cartilage damage or as a treatment for osteoarthritis, which causes the degeneration of joints. The latter is a very common condition, affecting one in four Swedes aged 45 and over.

At present, however, the structure of cellulose used in printed cartilage was ruled “not optimal” for the human body and needs to be fine-tuned before actually benefitting patients.

Source : https://goo.gl/JhMFYf

Make An Enquiry

We are here to help you

WordPress Video Lightbox