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 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

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  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.
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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

New research demonstrates that vitamin C targets and kills cancer stem cells, the cells responsible for cancer tumors growing and spreading. Researchers at the U.K.’s University of Salford found that vitamin C — ascorbic acid — was up to 10 times more effective in stopping cancer than experimental treatments.

“We have been looking at how to target cancer stem cells with a range of natural substances, but by far the most exciting are the results with vitamin C,” said Dr. Michael P. Lisanti.

Cancer stem-like cells are thought to be resistant to chemotherapy, which leads to treatment failure in patients with advanced disease. Researchers also believe that cancer stem cells (CSC) trigger the recurrence of tumors and fuel their growth. This allows them to spread throughout the body and cause death.

The Salford scientists set out to evaluate the bioenergetics of cancer stem cells — the processes which allow the cells to live and thrive — with the intent of disrupting their metabolism.

They studied the impact of seven substances: the clinically-approved epilepsy drug stiripentol, three natural products — caffeic acid phenethyl ester (CAPE), silibinin and ascorbic acid — and experimental pharmaceuticals actinonin, FK866 and 2-DG.

While they found that natural antibiotic actinonin and the compound FK866 were the most potent, the natural products also inhibited the formation of cancer stem cells, with vitamin C outperforming 2-DG 10-fold in terms of potency.

“Controlling cancer stem cells is the only way to control cancer and is a major weapon against metastatic cancer, which is the main killer of cancer patients,” neurosurgeon Dr. Russell Blaylock tells Newsmax Health.

“Conventional chemo and radiation can cure or control only 5 to 10 percent of metastatic cancers,” says Blaylock, author of Dr. Blaylock’s Prescriptions for Natural Health.

“Vitamin C is cheap, natural, non-toxic and readily available,” Lisanti said, “so to have it as a potential weapon in the fight against cancer would be a significant step.”

Lead author Gloria Bonuccelli said, “Our results indicate it is a promising agent for clinical trials, and as an add-on to more conventional therapies, to prevent tumor recurrence, further disease progression and metastasis.”

The effectiveness of vitamin C in fighting cancer has been hotly debated. Laboratory studies found that vitamin C killed cancer cells in the laboratory and also in mice, but similar results haven’t always been supported in human studies.

Experts speculate that contrary to laboratory and mice studies, most human studies have been conducted using oral vitamin C, and most is unused and excreted in urine. “The dose of vitamin C has to be very high,” says Blaylock. Very high doses are usually reached by IV infusion.

Until now, researchers have also believed that vitamin C’s anti-cancer potential is due to its antioxidant capabilities. However, researchers at the University of Iowa also found that vitamin C may actually work by generating free radicals that literally tear cancer cells apart while avoiding healthy cells.

A study published in Science found that vitamin C caused oxidative stress in cancer cells and turned off an enzyme cancer cells use to reproduce.

Vitamin C has also been shown to be effective in other areas of health:

• An analysis of 29 randomized human studies by scientists at Johns Hopkins found that a 500 milligram tablet of vitamin C each day significantly reduced both systolic and diastolic blood pressure.

• A European study of almost 20,000 men and women found that mortality from cardiovascular disease was 60 percent lower in people with the highest concentrations of vitamin C in their blood when compared to those with the lowest concentrations.

• A study published in The American Journal of Clinical Nutrition found that men with the lowest blood levels of vitamin C had a 62 percent higher risk of cancer-related death after a 12 to 16 year period, compared to those with the highest vitamin C levels.

• A Finnish study, which was published in Allergy, Asthma & Clinical Immunology, found that vitamin C halved the incidence and duration of the symptoms of bronchoconstriction, which causes symptoms of asthma during exercise. It also increased the post-exercise capacity of the lung’s small airways by 50 to 150 percent in more than 40 percent of asthmatics.

Source : https://goo.gl/WL2KzQ

World-first Transplant to Treat Macular Degeneration Could Augur Rise of iPS Cell Banks

On March 28, a Japanese man in his 60s became the first person to receive cells derived from induced pluripotent stem (iPS) cells that had been donated by another person.

The surgery is expected to set the path for more applications of iPS cell technology, which offers the versatility of embryonic stem cells without the latter’s ethical taint. Banks of iPS cells from diverse donors could make stem cell transplants more convenient to perform, while slashing costs.

iPS cells are created by removing mature cells from an individual (from their skin, for example), reprogramming these cells back to an embryonic state, and then coaxing them to become a cell type useful for treating a disease.

In the recent procedure, performed on a man from Hyogo prefecture, skin cells from an anonymous donor were reprogrammed and then turned into a type of retinal cell that was transplanted onto the retina of the patient who suffers from age-related macular degeneration. Doctors hope the cells will stop progression of the disease, which can lead to blindness.

In a procedure performed in September 2014 at the Kobe City Medical Center General Hospital, a Japanese woman received retinal cells derived from iPS cells. They were taken from her own skin, though, and then reprogrammed. Such cells prepared for a second patient were found to contain genetic abnormalities and never implanted.

The team decided to redesign the study based on new regulations, and no other participants were recruited to the clinical study. In February 2017, the team reported that the one patient had fared well. The introduced cells remained intact and vision had not declined as would usually be expected with macular degeneration.

In today’s procedure — performed at the same hospital and by the same surgeon Yasuo Kurimoto — doctors used iPS cells that had been taken from a donor’s skin cells, reprogrammed and banked. Japan’s health ministry approved the study, which plans to enroll 5 patients, on 1 February.

Using a donor’s iPS cells does not offer an exact genetic match, raising the prospect of immune rejection. But Shinya Yamanaka, the Nobel Prize-winning stem-cell scientist who pioneered iPS cells, has contended that banked cells should be a close enough match for most applications.

Yamanaka is establishing an iPS cell bank, which depends on matching donors to recipients via three genes that code for human leukocyte antigens (HLAs) — proteins on the cell surface that are involved in triggering immune reactions. His iPS Cell Stock for Regenerative Medicine currently has cell lines from just one donor. But by March 2018, they hope to create 5-10 HLA-characterized iPS cell lines, which should match 30%-50% of Japan’s population.

Use of these ready-made cells has advantages for offering stem cell transplants across an entire population, says Masayo Takahashi, an ophthalmologist at the RIKEN Center for Developmental Biology who devised the iPS cell protocol deployed in today’s transplant. The cells are available immediately — versus several months’ wait for a patient’s own cells — and are much cheaper. Cells from patients, who tend to be elderly, might have also accumulated genetic defects that could increase the risk of the procedure.

At a press conference after the procedure, Takahashi said the surgery had gone well but that success could not be declared without monitoring the fate of the introduced cells. She plans to make no further announcements about patient progress until all five procedures are finished. “We are at the beginning,” she says.

Source : https://goo.gl/Jyim9B

This statistic from the Centers for Disease Control and Prevention says it all: Approximately half of all American adults live with a chronic condition, and nearly one-third suffer from multiple. It’s no wonder, then, that chronic sicknesses significantly affect the American healthcare system.

Nowadays, Western medicine focuses on a disease’s specific symptoms, which mostly relieves symptoms or stops their progression. But persistent illness is a systemic problem that relates to a specific organ or several related ones.

Even if you relieve the problem, it’s only a temporary reprieve because the ailment will eventually recur and progress. Regeneration offers a means for eliminating chronic problems, preventively regenerating new cells, tissues, and even complete organs to return the body to its disease-free physiological state.

Stem Cell Therapy

For example, let’s examine chronic atrophic gastritis. A common gastrointestinal tract illness, CAG-induced pain is often treated with tablets that neutralize or adjust the GI’s environment. The condition, however, does destroy the cells in your stomach lining and cause metaplasia, which transforms or replaces them with acid-producing versions that live in your stomach.

Through regenerative rejuvenation, the metaplasia cells could be physiologically replaced by newly regenerated cells of the proper type. Eventually, all GI cell types and distribution will be able to maintain the same normal physiological state you had when you were young.

This is just one example of how regenerative rejuvenation works and how it can reduce the increasing financial burden on this country’s healthcare system. The onus of treatment shouldn’t just fall on doctors trying to find a cure.

Looking inward can enable us to replenish what’s already there. It can be a cost-efficient and less invasive version of recuperation.

Regenerating and Revitalizing the Future of Healthcare
Regenerative properties should be of specific interest to a population that’s doing exactly what it’s supposed to: getting older.

The CDC estimates the United States spends approximately $3 trillion in healthcare each year, about 17.5 percent of the country’s GDP. Chronic illness patients aged 65 and older are up to eight times more likely to incur these costs than those younger than 45.

Regenerative medicine holds the potential to curb those costs by providing more effective and affordable long-term solutions and an improved quality of life. Using the chronic GI illness mentioned above, regenerative medicine could renew a GI tract’s compromised mucosal layer. When it’s healthy, it’s more than capable of enduring both the basic and extremely acidic damage caused by internal fluid.

As people age, the GI mucosal layer becomes thinner, which can lead to chronic conditions such as inflammatory atrophic gastritis. Rather than focus on the symptoms of these conditions, physiological regeneration can restore the thickness and sustainability of the mucosal layer, preventing symptoms from recurring.

But regeneration isn’t just confined to chronic GI issues. Skin, as an external organ, is also susceptible to chronic pathological conditions that may be reversed with regenerative medicine. Physiological regeneration of traumatized tissue can prevent scar formation and potential disability. It can also halt the need for skin grafts that can lead to everlasting healthcare costs to maintain or improve your overall quality of life.

Regeneration isn’t just about getting overall healthcare costs under control; it’s about helping people — especially the chronically ill — enjoy the health and vitality of their youth, even into their golden years.

Exploring alternative means of treatment helps make that sustained contentedness possible. The examples above are just a few of the possibilities represented by regenerative medicine’s potential when utilized by those in need.

As more and more people contract or develop chronic illnesses, options outside the traditional treatment arena need to be explored. Make regeneration one avenue you take a long look at.

Source : https://goo.gl/uP3j9W

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