Posts tagged with "stem cells"

Derrick Wan, 360 MAGAZINE, stem cells

NEW STEM CELL STUDY

 A new study released today in STEM CELLS outlines how fat grafting – which previous studies have shown can reduce and even reverse fibrosis (scar tissue) buildup – also improves the range of motion of the affected limb. The study, conducted by researchers at Stanford University School of Medicine, was conducted on mice.

The tumor-destroying capabilities of radiation therapy can be a life saver for a person suffering from cancer. But it’s a therapy that has several unwanted side effects, too, including causing substantial damage not just to cancerous cells, but any healthy tissue in its path. Over time, fibrosis builds up in the treated area which, in the case of an arm, shoulder, or leg, for example, can lead to painful contractures that significantly limit extensibility and negatively impact the person’s quality of life.

The Stanford team irradiated the right hind legs of subject mice, which resulted in chronic fibrosis and limb contracture. Four weeks later, the irradiated limbs of one group of the mice were injected with fat enriched with stromal vascular cells (SVCs). These potent cells already naturally exist in fat, but supplementation of fat with additional SVCs enhances its regenerative capabilities. A second group was injected with fat only, a third group with saline and a fourth group received no injections, for comparison. The animals’ ability to extend their limb was then measured at baseline and every two weeks for a 12-week period. At the end of the 12 weeks, the hind limb skin underwent histological analysis and biomechanical strength testing.

“Each animal showed significant reduction in its limb extension ability due to the radiation, but this was progressively rescued by fat grafting,” reported corresponding author Derrick C. Wan, M.D., FACS. Fat grafting also reduced skin stiffness and reversed the radiation-induced histological changes in the skin.

“The greatest benefits were found in mice injected with fat enriched with SVCs,” Dr. Wan added. “SVCs are easily obtained through liposuction and can be coaxed into different tissue types, where they can support neovascularization, replace cells and repair injured issue.

“Our study showed the ability of fat to improve mobility as well as vascularity and appearance,” he continued. “We think this holds enormous clinical potential — especially given that adipose tissue is abundant and can be easily collected from the patients themselves — and underscores an attractive approach to address challenging soft tissue fibrosis in patients following radiation therapy.”

Furthermore, said co-author and world-renowned breast reconstructive expert Arash Momeni, M.D., FACS, “Our observations are potentially translatable to a variety of challenging clinical scenarios. Being able to reverse radiation-induced effects holds promise to substantially improve clinical outcomes in implant-based as well as autologous breast reconstruction. The study findings are indeed encouraging as they could offer patients novel treatment modalities for debility clinical conditions.

“Excessive scarring is a challenging problem that is associated with a variety of clinical conditions, such as burn injuries, tendon lacerations, etc. The potential to improve outcomes based on treatment modalities derived from our research is indeed exciting,” Dr. Momeni added.

“Skin and soft tissue scarring and fibrosis are well-established problems after radiation. The current study, showing that human fat grafting can normalize the collagen networks and improve tissue elasticity in immune deficient mice, provides molecular evidence for how fat grafting functions,” said Dr. Jan Nolta, Editor-in-Chief of STEM CELLS. “The studies indicate that, with the appropriate regulatory approvals, autologous fat grafting could potentially also help human patients recover from radiation-induced tissue fibrosis.”

Full article HERE.

Stem Cell Relief

Clinical trial shows promise of stem cells in offering safe, effective relief from arthritic knees

Stem cells collected from the patient’s own bone marrow holds great interest as a potential therapy for osteoarthritis of the knee (KOA) because of their ability to regenerate the damaged cartilage. The results were released today in STEM CELLS Translational Medicine (SCTM).

KOA is a common, debilitating disease of the aging population in which the cartilage wears away, resulting in bone wearing upon bone and subsequently causing great pain. In its end stages, joint replacement is currently the recommended treatment. In the first clinical trial of its kind to take place in Canada, researchers used mesenchymal stromal cells (MSCs), collected from the patient’s own bone marrow under local anesthesia, to treat KOA.

The study was conducted by a research team from the Arthritis Program at the Krembil Research Institute, University Health Network, Toronto, led by Sowmya Viswanathan, Ph.D., and Jaskarndip Chahal, M.D. “Our goal was to test for safety as well as to gain a better understanding of MSC dosing, mechanisms of action and donor selection,” Dr. Viswanathan said.

It involved 12 patients, aged 45 to 65, with moderate to severe KOA. They were divided into three groups, with each group receiving a different dose of MSCs. (Each patient was injected with his or her own cells.) The researchers then followed the patients for the next 12 months, using analytical methods that included imaging, biomarkers, molecular fingerprinting and the patient’s own assessment of how he or she felt.

At the end of the 12-month period, the team noted significant improvements in the patients’ pain levels and quality of life. The study also showed that the MSCs were safe at all the doses tested and that the higher the dose, the more effective the outcome.

Dr. Viswanathan said, “We also obtained novel insights into a potential anti-inflammatory mechanism of action of these cells in osteoarthritic knee joints. We noted that donor heterogeneity is an important factor, and our assembled panel of genes helps us identify cells which are potent in osteoarthritis. These are important findings which we hope to translate into a larger, powered clinical trial as part of our next steps.”  

“Furthermore,” added Dr. Chahal, “we have been able to show that through an anti-inflammatory mechanism of action, such patients have an improvement in pain, function and quality of life. This sets the stage for the future of cell-based therapy and trials in Canada.”

“This clinical pilot study advances the field of stem cell research for patients with arthritis, showing safety, and giving insights into potential therapy efficacy guidelines”, said Anthony Atala, M.D., Editor-in-Chief of STEM CELLS Translational Medicine and director of the Wake Forest Institute for Regenerative Medicine. “We look forward to larger scale trial results.”

The full article, “Bone Marrow Mesenchymal Stromal Cells in Patients with Osteoarthritis Results in Overall Improvement in Pain and Symptoms and Reduces Synovial Inflammation,” can be accessed here.

About STEM CELLS Translational Medicine

STEM CELLS Translational Medicine (SCTM), co-published by AlphaMed Press and Wiley, is a monthly peer-reviewed publication dedicated to significantly advancing the clinical utilization of stem cell molecular and cellular biology. By bridging stem cell research and clinical trials, SCTM will help move applications of these critical investigations closer to accepted best practices. SCTM is the official journal partner of Regenerative Medicine Foundation.

About AlphaMed Press

Established in 1983, AlphaMed Press with offices in Durham, NC, San Francisco, CA, and Belfast, Northern Ireland, publishes two other internationally renowned peer-reviewed journals: STEM CELLS® , celebrating its 37th year, is the world’s first journal devoted to this fast paced field of research. The Oncologist® also a monthly peer-reviewed publication, entering its 24th year, is devoted to community and hospital-based oncologists and physicians entrusted with cancer patient care. All three journals are premier periodicals with globally recognized editorial boards dedicated to advancing knowledge and education in their focused disciplines.  

About Wiley

Wiley, a global company, helps people and organizations develop the skills and knowledge they need to succeed. Our online scientific, technical, medical and scholarly journals, combined with our digital learning, assessment and certification solutions, help universities, learned societies, businesses, governments and individuals increase the academic and professional impact of their work. For more than 200 years, we have delivered consistent performance to our stakeholders. The company’s website can be accessed here.

About Regenerative Medicine Foundation (RMF)

The non-profit Regenerative Medicine Foundation fosters strategic collaborations to accelerate the development of regenerative medicine to improve health and deliver cures. RMF pursues its mission by producing its flagship World Stem Cell Summit, honoring leaders through the Stem Cell and Regenerative Medicine Action Awards, and promoting educational initiatives.

Stem Cells & Transitional Medicine

Study is first to indicate impact of donor age on stem cell therapy for spinal cord injuries

The potential for stem cells to reduce damage, regenerate tissue and promote functional recovery after a spinal cord injury (SCI) is being tested in several ongoing clinical trials. However, a new study released today in STEM CELLS Translational Medicine (SCTM) indicates that donor age-dependent stem cell therapy could help optimize cell treatment strategies for clinical translation.

“To our knowledge, this is the first study to compare mesenchymal stromal cells derived from different donor ages and sources, and the first to identify similarities and differences between how these cells affect tissue regeneration and key functional parameters after a traumatic SCI,” said Michael Fehlings, M.D., Ph.D. Dr. Fehlings led the team of investigators from the University of Toronto and Krembil Research Institute, University Health Network in conducting the study.

Every year as many as 500,000 people worldwide suffer a SCI, according to the World Health Organization. Damage to the circulatory system after such an injury can trigger a cascade of secondary events, including inflammation and scarring. Mesenchymal stromal cells (MSCs) — which are stem cells isolated from bone marrow, adipose and other adult tissue sources, as well as the umbilical cord, that can differentiate into a variety of cells types — also possess characteristics common to pericytes (cells that support blood vessel integrity). These features add up to make MSCs ideal candidates for treating SCI. As such, several clinical trials are currently underway testing how infusions of bone marrow-derived stem cells (BMSCs) affect SCI.

What was not being investigated until the study reported on in SCTM, however, is whether the age of the cell donor can have an impact on treatment outcome. Clifford Librach, M.D., FRCS(C), also a professor at the University of Toronto, whose team did the pioneering work on the use of early pregnancy umbilical cord-derived human umbilical perivascular cells (HUCPVCs) for regenerative therapy, approached Dr. Fehlings with the novel idea to use these cells in his rodent model of SCI.  This developed into a unique collaboration between a reproductive biologist and a neurosurgeon/neuroscientist. On this project Dr. Fehlings’ team tackled this question using HUCPVCs collected at two different stages – full-term and first trimester, provided by Dr. Librach’s team. They then compared them to adult BMSCs and a control vehicle. The team chose HUCPVCs for their study as they tend to exhibit greater proliferative potential in culture and, once implanted, have better rates of survival, migration and integration with the host’s central nervous system than BMSCs.

The team conducted their test on adult rats, starting the cell infusions an hour after the animals had undergone a spinal cord injury. The results, taken 10 weeks later, showed that the younger the cell source, the better the outcome. Both HUCPVC age groups outperformed the BMSCs and the control.

“By examining the effects of donor cell age and source, this study brings us closer to understanding the ways in which mesenchymal stromal cells work to improve outcome after spinal cord injury and maximising their therapeutic potential.” said Reaz Vawda, Ph.D., co-author of the study.

When it came to reducing neurovascular disruption, astrogliosis and scarring, the first trimester HUCPVCs slightly outperformed the full term HUCPVCs. “As far as improving the animals’ functional ability, the first trimester HUCPVC was the only cell type that resulted in lasting chronic effects in forelimb function and weight gain,” said Dr. Librach.

“This study demonstrates a clear age-related difference in cell efficacy after SCI, with first trimester cells outperforming term cells,” Dr. Fehlings reported. “Additionally, we applied an innovative ultrasound technique to accurately measure acute lesional volume and, later, cavitation (whereby a SCI can expand in size leading to a scar-encapsulated cavity many times the size of the initial injury) in live animals.

“Together, this minimally invasive and effective approach to cell therapy has significant implications on the treatment of traumatic cervical SCI and other central nervous system injuries,” he added. “These results can help to optimize cell treatment strategies for eventual use in humans.”

“Outcomes from this first-of-its-kind study are advancing what we already know about mesenchymal stromal cells and their healing potential for traumatic spinal cord injury by comparing different donor ages and sources, providing new information about their therapeutic efficacy,” said Anthony Atala, M.D., Editor-in-Chief of STEM CELLS Translational Medicine and director of the Wake Forest Institute for Regenerative Medicine. “We look forward to seeing how these results impact treatment strategies for clinical translation to ultimately help the half million people worldwide who suffer this type of injury.”

The full article, “Early intravenous infusion of mesenchymal stromal cells exerts a tissue source age-dependent beneficial effect on neurovascular integrity and neurobehavioural recovery after traumatic cervical spinal cord injury,” can be accessed here.

About Stem Cells

Translational Medicine: STEM CELLS Translational Medicine (SCTM), co-published by AlphaMed Press and Wiley, is a monthly peer-reviewed publication dedicated to significantly advancing the clinical utilization of stem cell molecular and cellular biology. By bridging stem cell research and clinical trials, SCTM will help move applications of these critical investigations closer to accepted best practices. SCTM is the official journal partner of Regenerative Medicine Foundation.

About AlphaMed Press

Established in 1983, AlphaMed Press with offices in Durham, NC, San Francisco, CA, and Belfast, Northern Ireland, publishes two other internationally renowned peer-reviewed journals: STEM CELLS® , celebrating its 37th year, is the world’s first journal devoted to this fast paced field of research. The Oncologist® also a monthly peer-reviewed publication, entering its 24th year, is devoted to community and hospital-based oncologists and physicians entrusted with cancer patient care. All three journals are premier periodicals with globally recognized editorial boards dedicated to advancing knowledge and education in their focused disciplines.

About Wiley

Wiley, a global company, helps people and organizations develop the skills and knowledge they need to succeed. Our online scientific, technical, medical and scholarly journals, combined with our digital learning, assessment and certification solutions, help universities, learned societies, businesses, governments and individuals increase the academic and professional impact of their work. For more than 200 years, we have delivered consistent performance to our stakeholders. The company’s website can be accessed at here.

About Regenerative Medicine Foundation (RMF)

The non-profit Regenerative Medicine Foundation fosters strategic collaborations to accelerate the development of regenerative medicine to improve health and deliver cures. RMF pursues its mission by producing its flagship World Stem Cell Summit, honoring leaders through the Stem Cell and Regenerative Medicine Action Awards, and promoting educational initiatives.

Endothelial progenitor cells for treating stroke patients

A new study recently published in STEM CELLS Translational Medicine demonstrates the long-term safety of laboratory-expanded endothelial progenitor cells for treating ischemic stroke. This could be good news for the 15 million people who, according to to the World Stroke Organization, suffer from this dangerous condition each year.

Ischemic stroke is the most common type of stroke, affecting nearly 90 percent of all cases. It is caused by a blocked blood vessel in the brain. In the normal central nervous system, endothelial progenitor cells (EPCs) play an active role in building blood vessels. This has led researchers to wonder whether EPCs circulating in the blood could be recruited after a stroke to assist in repairing damaged vessels in the brain. However, there is one major problem with this idea: The number of circulating EPCs is too low to provide much regenerative capacity – a number that further decreases in the aging or in those with heart problems.

This makes ex vivo (lab) expanded EPCs an attractive alternative.

“Transplantation of EPCs was already determined in animal experiments to be a safe and effective method for treating ischemic stroke. However, their safety and efficacy had yet to be determined in humans,” said Zhenzhou Chen, M.D., Ph.D., Southern Medical University, Guangzhou, China, and a corresponding author on the study. “In our trial, we tested the safety and feasibility of transplanting an acute ischemic stroke patient with his or her own (autologous) ex vivo expanded EPCs.”

Eighteen patients were recruited for the randomized, single-blinded study. Each received conventional treatment after their stroke then, seven days after symptom onset, underwent a bone marrow aspiration to collect EPCs and bone marrow stromal cells (BMSCs) for expansion in the lab. The patients were divided into three groups and, beginning at week four after the aspiration, one group was intravenously infused with their own EPCs, while the other two groups received either their own BMSCs or a saline placebo as the controls.

Each patient was then monitored for 48 months. Study co-author Xiaodan Jiang, M.D., Ph.D., also from Southern Medical University, explained, “We watched for mortality of any cause, adverse events and any new-onset diseases or conditions. Changes in neurological deficits were also assessed at different time points.”

In the end the researchers found no toxicity events nor did they see any infusional or allergic reactions in any of the patients. “The EPC group had less serious adverse events compared to the placebo-controlled group, although there were no statistical differences in mortality among the three groups,” Dr. Chen reported. “Ex vivoexpansion always raises concerns that it may cause instability in the chromosomes or maybe lead to tumors. However, in our long-term study we observed no increased tumorigenicity. This safety indicator was also confirmed by many animal studies and other trials using expanded bone marrow-derived stem cells for treatment of ischemic stroke.”

The researchers did note limitations in their study, including lack of patient-centered quality of life outcomes. “Moreover, because of the small size of the cohorts involved, we could neither identify the neurological or functional benefits of EPCs on ischemic stroke, nor determine the pros and cons between EPCs and BMSCs for stroke treatment,” Dr. Jiang said. “Thus, we believe a larger phase 2 trial is warranted.”

“This is a promising line of cell therapy research using a novel treatment method that is simple and non-invasive,” said Anthony Atala, M.D., Editor-in-Chief of STEM CELLS Translational Medicine and director of the Wake Forest Institute for Regenerative Medicine. “We look forward to larger phase 2 trial results.”

The full article, “Autologous endothelial progenitor cells transplantation for acute ischemic stroke: A four-year follow-up study,” can be accessed at http://www.stemcellstm.com.

About STEM CELLS Translational Medicine: STEM CELLS Translational Medicine (SCTM), published by AlphaMed Press, is a monthly peer-reviewed publication dedicated to significantly advancing the clinical utilization of stem cell molecular and cellular biology. By bridging stem cell research and clinical trials, SCTM will help move applications of these critical investigations closer to accepted best practices. SCTM is the official journal partner of Regenerative Medicine Foundation.

About AlphaMed Press: Established in 1983, AlphaMed Press with offices in Durham, NC, San Francisco, CA, and Belfast, Northern Ireland, publishes two other internationally renowned peer-reviewed journals: STEM CELLS® (www.StemCells.com), celebrating its 36th year, is the world’s first journal devoted to this fast paced field of research. The Oncologist® (www.TheOncologist.com), also a monthly peer-reviewed publication, entering its 23rd year, is devoted to community and hospital-based oncologists and physicians entrusted with cancer patient care. All three journals are premier periodicals with globally recognized editorial boards dedicated to advancing knowledge and education in their focused disciplines.

About Wiley: Wiley, a global company, helps people and organizations develop the skills and knowledge they need to succeed. Our online scientific, technical, medical and scholarly journals, combined with our digital learning, assessment and certification solutions, help universities, learned societies, businesses, governments and individuals increase the academic and professional impact of their work. For more than 200 years, we have delivered consistent performance to our stakeholders. The company’s website can be accessed at www.wiley.com.

About Regenerative Medicine Foundation (RMF): The non-profit Regenerative Medicine Foundation fosters strategic collaborations to accelerate the development of regenerative medicine to improve health and deliver cures. RMF pursues its mission by producing its flagship World Stem Cell Summit, honouring leaders through the Stem Cell and Regenerative Medicine Action Awards, and promoting educational initiatives.