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Long term effect and safety of Wharton’s jelly-derived mesenchymal stem cells on type 2 diabetes

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While updating my database of human clinical trials using expanded human umbilical cord mesenchymal cells I came across a new article (April, 2016) describing a 36-month safety in subjects given intravenous cells for in a type 2 diabetes study. The study, a phase I/II, 36‑month, randomized controlled trial was conducted in patients diagnosed with T2DM according to the criteria outlined by the American Diabetes Association and performed at Qingdao University by Dr. Jianxia Hu et. al. 1 Not only were there no adverse events in the treatment group of 31 subjects but there were significant improvements in blood sugar control and decreased diabetes-related complications.

Two intravenous infusions of expanded human umbilical cord mesenchymal stem cells were given four weeks apart. The dose of each infusion was based on the weight of the subjects and averaged 60 million cells.

Significant improvements were seen in post-prandial glucose and hemoglobin A-1C levels but not fasting glucose.

Adapted from Figure 2 of Hu et al. 2016 Long term effect and safety of Wharton’s jelly-derived mesenchymal stem cells on type 2 diabetes.Exp Ther Med. 2016 Sep; 12(3): 1857–1866 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4997981/

 

C-peptide (surrogate for endogenous insulin production) and C-peptide to glucose ratio were both significantly improved in the treatment group.

 

Adapted from Figure 3 of Hu et al. 2016 Long term effect and safety of Wharton’s jelly-derived mesenchymal stem cells on type 2 diabetes.Exp Ther Med. 2016 Sep; 12(3): 1857–1866 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4997981/

 

 

Significant improvement was seen in the HOMA‑β, homeostasis model assessment of pancreatic islet β‑cell function; while there was no improvement in the HOMA‑IR, homeostasis model assessment of insulin resistance.

The improvements seemed to peak between 15 and 21 months after treatment supporting a rationale for re-treatment before 15 months.

 

  1. JIANXIA HU, YANGANG WANG, HUIMIN GONG, CHUNDONG YU, CAIHONG GUO, FANG WANG, SHENGLI YAN and HONGMEI XU. Long term effect and safety of Wharton’s jelly-derived mesenchymal stem cells on type 2 diabetes. EXPERIMENTAL AND THERAPEUTIC MEDICINE 12: 1857-1866, 2016. Stem Cell Research Center, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003

 

 

Treatment with Mesenchymal Stem Cells Shown to be Safe for Dog Muscular Dystrophy

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Duchenne Muscular Dystrophy (DMD) is a degenerative genetic disorder that affects the muscles in the body in a progressive manner, leading to eventual death. Mesenchymal stem cells (MSC) are able to reach the affected muscle cells and to start tissue regeneration and repair, making them an attractive treatment option for DMD. This study by Pelatti et al. demonstrates the safety of MSC to treat Golden Retriever Muscular Dystrophy – an animal disorder with remarkable similarities to human dystrophy. The treatment was well-tolerated and no long-term adverse effects were reported.

Stem Cell Rev. 2016 May 19. doi: 10.1007/s12015-016-9659-3

Transplantation of Human Adipose Mesenchymal Stem Cells in Non-Immunosuppressed GRMD Dogs is a Safe Procedure.

Pelatti MV, Gomes JP, Vieira NM, Cangussu E, Landini V, Andrade T, Sartori M, Petrus L, Zatz M.

Abstract

The possibility to treat Duchenne muscular dystrophy (DMD), a lethal X-linked disorder, through cell therapy with mesenchymal stromal cells (MSCs) has been widely investigated in different animal models. However, some crucial questions need to be addressed before starting human therapeutic trials, particularly regarding its use for genetic disorders. How safe is the procedure? Are there any side effects following mesenchymal stem cell transplantation? To address these questions for DMD the best model is the golden retriever muscular dystrophy dog (GRMD), which is the closest model to the human condition displaying a much longer lifespan than other models. Here we report the follow-up of 5 GRMD dogs, which were repeatedly transplanted with human adipose-derived mesenchymal stromal cells (hASC), derived from different donors. Xenogeneic cell transplantation, which was done without immunosuppression, was well tolerated in all animals with no apparent long-term adverse effect. In the present study, we show that repeated heterologous stem-cell injection is a safe procedure, which is fundamental before starting human clinical trials.

PMID: 27193781

Umbilical Cord Mesenchymal Stem Cells as Preeclampsia Treatment

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Treatment with human umbilical cord mesenchymal stem cells is shown to be effective in controlling hypertension and reducing the infiltration of inflammatory cells in the placenta, in this preeclampsia rat model.

Reprod Sci. 2016 Feb 17. pii: 1933719116630417.

Effect of Human Umbilical Cord Mesenchymal Stem Cell Transplantation in a Rat Model of Preeclampsia.

Wang LL, Yu Y, Guan HB, Qiao C.

Abstract

OBJECTIVE: To test the effects of human umbilical cord mesenchymal stem cell (HU-MSC) transplantation on reversing preeclampsia (PE) symptoms in a lipopolysaccharide (LPS)-induced rat PE model.

METHODS: Human umbilical cord MSCs were detected, isolated, and cultured. Human umbilical cord MSC transplantation was conducted. Expressions of inflammatory cytokines in serum and placental tissue were measured by enzyme-linked immunosorbent assay. Changes in inflammatory cytokines, peroxisome proliferator-activated receptor γ (PPARγ), laminin receptor 1 (LR1), matrix metalloproteinase (MMP) 2, and MMP-9 messenger RNA (mRNA) levels in placental tissue were recorded by quantitative real-time polymerase chain reaction. Immunohistochemistry and Western blotting were performed for PPARγ detection.

RESULTS: The LPS group exhibited increased blood pressure and proteinuria and decreased fetal weight compared to the normal pregnancy (NP) group (all P < .05). The LPS + MSC group presented lowered blood pressure and higher fetal weight than the LPS group (P < .05). The levels of interferon γ, tumor necrosis factor α (TNF-α), interleukin (IL) 1β, IL-6, IL-8, IL-12, and intercellular adhesion molecule 1 (ICAM-1) increased and the levels of IL-4 and IL-10 levels decreased in the LPS group compared to the NP group (all P < .05). Tumor necrosis factor α, IL-6, IL-12, and ICAM-1 levels decreased and IL-10 level increased in the LPS + MSC group compared to the LPS group (all P < .05). The LPS-MSC group showed lower mRNA expressions of TNF-α, IL-6, MMP-2, MMP-9, and ICAM-1 and higher mRNA expressions of IL-10, PPARγ, and LR1 than the LPS group (all P < .05).

CONCLUSION: In summary, HU-MSC transplantation may be extremely beneficial for PE therapy.

© The Author(s) 2016.

PMID: 26887428

 

Umbilical cord MSC treatment improves liver condition in rat acute liver failure

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Human umbilical cord mesenchymal stem cells (hUCMSC) were found to improve liver condition in rats after acute liver failure, slowing the degeneration of liver cells. The results were comparable whether treatment was administered intravenously or via intrahepatic injection.

Int J Clin Exp Pathol. 2015 Dec 1; 8(12):15854-62.

Transplantation of umbilical cord mesenchymal stem cells via different routes in rats with acute liver failure.

Zheng S, Yang J, Yang J, Tang Y, Shao Q, Guo L, Liu Q.

Abstract

OBJECTIVE: This study aimed to compare the therapeutic efficacy of transplantation of human umbilical cord mesenchymal stem cells (hUCMSC) in different routes in acute hepatic failure (ALF) in rats.

METHODS: hUCMSCs were isolated and identified by detection of surface antigens via flow cytometry. In T group and H group, ALF rats received hUCMSC transplantation through the tail vein and intrahepatic injection, respectively. In hUCMSC group, healthy rats received hUCMSCs transplantation via the tail vein. In ALF group, rats received injection of normal saline through the tail vein.

RESULTS: The TBil and ALT in ALF rats with and without transplantation were significantly higher than in healthy rats (P<0.05). HE staining of the liver showed obvious hepatocyte regeneration and reduced infiltration of inflammatory cells, and liver pathology was improved in T group and H group as compared to ALF group. At 3 d after transplantation, CK18 expression was detectable in both H group and T group. At 1 w and 2 w, the mRNA expressions of CK8, CK18 and AFP in H group and T group were significantly different from those in ALF group (P<0.05). The liver function and differentiation of stem cells were comparable between H group and T group (P>0.05).

CONCLUSION: hUCMSCs transplantation can improve the liver function and promote the liver repair following ALF. hUCMSCs transplantation via tail vein has similar therapeutic efficacy to that through intrahepatic injection.

PMID: 26884856

PMCID: PMC4730069

 

Human CD34 improves locomotor function in spinal cord injury rats

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In this new 2016 study, rats with spinal cord injury (SCI) were treated with conditioned medium or secretome obtained from human CD34 umbilical cord stem cells. Locomotor function was improved; in particular, neurological deficits, cell death, extent of inflammation, oxidative stress and astrogliosis were attenuated.

These findings corroborate our results published in 2010 – a spinal cord injury patient reported decreases in neuropathic pain and ASIA scores, recovery of muscle, bowel and sexual function, following treatment with umbilical cord CD34 and stem cells. 

Taiwan J Obstet Gynecol. 2016 Feb;55(1):85-93. doi: 10.1016/j.tjog.2015.12.009.

Attenuating spinal cord injury by conditioned medium from human umbilical cord blood-derived CD34(+) cells in rats.

Yeng CH, Chen PJ, Chang HK, Lo WY, Wu CC, Chang CY, Chou CH, Chen SH.

Abstract

OBJECTIVE:

Intravenous or intraspinal transplantation of human umbilical cord blood cells-derived CD34(+) cells (human CD34(+) cells) or mesenchymal stem cells after spinal cord injury (SCI) improved hind limb functional recovery in adult rats. The objective of this study is to ascertain whether SCI in rats can be attenuated by conditioned medium (CM) or secretome obtained from cultured human CD34(+) stem cells.

MATERIALS AND METHODS:

Sprague-Dawley rats were assigned to one of the following five groups: the sham group, the SCI group treated with vehicle solution (SCI + V), the SCI group treated with CM (SCI + CM), the SCI group treated with 17β-estradiol E2 (10 μg; SCI + E2), and the SCI group treated with CM plus E2 (SCI + CM + E2). A 0.5-mL volume of CM or vehicle solution was administered intravenously immediately after SCI.

RESULTS:

Compared with the sham group, the (SCI + V) group had significantly higher scores of neurological motor dysfunction as well as inflammation apoptosis, oxidative stress, and astrogliosis in the injured spinal cord. The neurological deficits, numbers of apoptotic cell, extent of inflammation, oxidative stress, and astrogliosis in the injured spinal cord were significantly attenuated by CM, E2, or CM plus E2, but not by the vehicle solution. In addition, the neuroprotective effect exerted by a combination of CM and E2 is superior to that exerted by CM- or E2-alone therapy.

CONCLUSION:

The neuroprotective effects of CM from cultured human CD34(+) cells are similar to those of human CD34(+) cells and the CM was found to enhance the neuroprotective effects of E2 in rat SCI.

Copyright © 2016. Published by Elsevier B.V.

PMID: 26927256

Panama’s First Umbilical Cord Stem Cell Clinical Trial for Rheumatoid Arthritis

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Press release

Panama’s First Umbilical Cord Stem Cell Clinical Trial for Rheumatoid Arthritis Approved by Comité Nacional de Bioética de la Investigación Institutional Review Board
Translational Biosciences, a subsidiary of Medistem Panama has received the county’s first clinical trial approval for the treatment of rheumatoid arthritis with human umbilical cord-derived mesenchymal stem cells (MSC) from the Comité Nacional de Bioética de la Investigación (CNEI) Institutional Review Board (IRB).

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Panama City, Panama (PRWEB) January 14, 2014

Translational Biosciences, a subsidiary of Medistem Panama has received the county’s first clinical trial approval for the treatment of rheumatoid arthritis with human umbilical cord-derived mesenchymal stem cells (MSC) from the Comité Nacional de Bioética de la Investigación Institutional Review Board (IRB).
Rheumatoid Arthritis (RA) is an autoimmune disease in which the patient’s immune system generates cellular and antibody responses to various components of the joint such as type I collagen. As a result of this immune response, not only does joint destruction occur, but also other secondary complications such as pulmonary fibrosis, renal damage, and even heart damage. RA affects approximately 0.5-1% of the population in the United States.
Mesenchymal stem cells harvested from donated human umbilical cords after normal, healthy births possess anti-inflammatory and immune modulatory properties that may relieve RA symptoms. Because they are immune privileged, the recipient’s immune system does not reject them. These properties make MSC interesting candidates for the treatment of rheumatoid arthritis and other autoimmune disorders.
Each patient will receive five intravenous injections of umbilical cord stem cells over the course of 5 days. They will be assessed at 3 months and 12 month primarily for safety and secondarily for indications of efficacy.
The stem cell technology being utilized in this trial was developed by Neil Riordan, PhD, founder of Medistem Panama. The stem cells will be harvested and processed at Medistem Panama’s 8000 sq. ft. laboratory in the prestigious City of Knowledge. They will be administered at the Stem Cell Institute in Panama City, Panama.
The Principle Investigator is Jorge Paz-Rodriguez, MD. Dr. Paz-Rodriguez also serves as the Medical Director at the Stem Cell Institute.
“While this is just the first step, it is our hope that Panama’s rapid emergence as a leader in applied stem cell research will lead to safe, effective treatments for debilitating diseases such as rheumatoid arthritis and serve to benefit all Panamanians who suffer from it in the not-too-distant future,” said Ruben Berocal, M.D., National Secretary of Science, Technology and Innovation (SENACYT). “Oversight by the National Committee for Investigational Bioethics ensures patient safety by demanding ethical transparency and compliance with the highest levels of international standards,” he added.
For detailed information about this clinical trial visit http://www.clinicaltrials.gov. If you are a rheumatoid arthritis patient who has not responded to disease modifying anti-rheumatic drugs (DMARD) for at least 6 months you may qualify for this trial. Please email trials(at)translationalbiosciences(dot)com for more information about how to apply.
About Translational Biosciences
A subsidiary of Medistem Panama Inc., Translational Biosciences was founded solely to conduct clinical trials using adult stem cells and adult stem cell-derived products.
Translational Biosciences Web Site: http://www.translationalbiosciences.com
Email: trials(at)translationalbiosciences(dot)com
About Medistem Panama Inc.
Since opening its doors in 2007, Medistem Panama Inc. has developed adult stem cell-based products from human umbilical cord tissue and blood, adipose (fat) tissue and bone marrow. Medistem operates an 8000 sq. ft. ISO 9001-certified laboratory in the prestigious City of Knowledge. The laboratory is fully licensed by the Panamanian Ministry of Health and features 3 class 10000 clean rooms, class 100 laminar flow hoods, and class 100 incubators.
Medistem Panama Inc.
Ciudad del Saber, Edif. 221 / Clayton
Panama, Rep. of Panama
Phone: +507 306-2601
Fax: +507 306-2601
About Stem Cell Institute Panama
Founded in 2007 on the principles of providing unbiased, scientifically-sound treatment options, the Stem Cell Institute has matured into the world’s leading adult stem cell therapy and research center. In close collaboration with universities and physicians world-wide, our comprehensive stem cell treatment protocols employ well-targeted combinations of autologous bone marrow stem cells, autologous adipose stem cells, and donor human umbilical cord stem cells to treat: multiple sclerosis, spinal cord injury, osteoarthritis, rheumatoid arthritis, heart disease, and autoimmune diseases. To-date, the Institute has treated over 2000 patients.
For more information on stem cell therapy:
Stem Cell Institute Website: http://www.cellmedicine.com
Stem Cell Institute
Via Israel & Calle 66
Plaza Pacific Office #2A
Panama City, Panama
Phone: +1 800 980-STEM (7836) (USA Toll-free) +1 954 636-3390 (from outside USA)
Fax: +1 866 775-3951 (USA Toll-free) +1 775 887-1194 (from outside USA)