Stem Cells Embedded in a Fibrin Patch Help Hearts Recover After a Heart Attack


If a patient has a heart failure, there is little you can do for them. Medications can take some of the stress off the failing heart, and in extreme cases, a heart transplant is warranted. However, organ transplants are hampered by both the limited number of organ donors and the potential for the patient’s body to reject the new heart.

A new study from the journal STEM CELLS Translational Medicine has shown that heart tissue can be regenerated if engineered patches made up of a mixture of fibrin and mesenchymal stem cells (MSCs) derived from human umbilical cord blood are applied to the heart.

Previous studies show the potential of MSCs to repair damage generated by a heart attack. In these clinical studies, the MSCs were delivered through injections into the heart muscle or intravenously. “While feasible and safe, the treatments exhibited only modest benefits,” said Antoni Bayes-Genis, M.D., Ph.D., member of the ICREC (Heart Failure and Cardiac Regeneration) Research Program, Germans Trias i Pujol Health Science Research Institute (IGTP) and professor at Universitat Auto`noma de Barcelona. Dr. Bayes-Genis is a lead investigator on this study.

“The survival rate of the implanted stem cells was generally low and about 90 percent of them either died or migrated away from the implantation site, generally to the liver,” added the study’s first author, Santiago Roura, Ph.D., also a member of the ICREC Research Program and IGTP. “These limited effects are probably due to the adverse mechanical stress and hypoxic conditions present in the myocardium after the heart attack.”

Now could a better way to deliver the MSCs to the injured site yield more efficient results? Synthetic scaffolds (or patches) in which the cells are embedded in matrices constructed of biological and/or synthetic materials and supplemented with growth or differentiation factors can generate so-called “bioimplants.” Bioimplants are a promising way to potentially apply stem cells to the heart in a way that will allow them to survive, grow and thrive. Unfortunately, none of the current materials being tested for heart patches, whether synthetic or natural has been shown to provide optimal properties for cardiac tissue repair.

Dr. Bayes-Genis and his colleagues examined how a fibrin patch filled with human umbilical cord blood-derived MSCs might serve to repair a damaged heart. Fibrin is widely used in medical applications, since it can act as a bio-compatible glue that holds cells in place and stimulating the production of new blood vessels (angiogenesis). Bayes-Genis and others hypothesized that fibrin scaffolds might offer a nurturing environment for the growth and proliferation of MSCs at the site of the heart injury. There, the cells could induce the repair of damaged heart tissue.

Bayes-Genis and coworkers mixed MSCs and fibrin to form the patches that were then applied to the hearts of mice that had undergone heart attacks. Three weeks later, they compared the recovery of these animals to a control group of mice that were treated with fibrin alone without embedded stem cells, and a third group that received no treatment at all. The results showed that the patches adhered well to the hearts and the MSCs grew and differentiated. The patch cells also participated in the formation of new, functional blood vessels that connected the patch to both the heart tissue directly beneath it and the mouse’s endogenous circulatory system, too.

“As a result, the heart function in this group of mice was better than that of the animals in either of the other control groups,” Dr. Bayes-Genis said. “Thus, this study provides promising findings for the use of umbilical cord-blood MSCs and fibrin patches in cardiac repair.”

“This is an interesting study that suggests a news strategy for using stem cells to repair injured heart tissue, without the drawbacks that cell injections have shown,” said Anthony Atala, M.D., Editor-in-Chief of STEM CELLS Translational Medicine and Director of the Wake Forest Institute for Regenerative Medicine.

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Amniotic Fluid Stem Cells Make Robust Blood Vessel Networks


The growth of new blood vessels in culture received in new boost from researchers at Rice University and Texas Children’s Hospital who used stem cells from amniotic fluid to promote the growth of robust, functional blood vessels in healing hydrogels.

These results were published in the Journal of Biomedical Materials Research Part A.

Engineer Jeffrey Jacot thinks that amniotic fluid stem cells are valuable for regenerative medicine because of their ability to differentiate into many other types of cells, including endothelial cells that form blood vessels. Amniotic fluid stem cells are taken from the discarded membranes in which babies are encased in before birth. Jacot and others combined these cells with an injectable hydrogel that acted as a scaffold.

In previous experiments, Jacot and his colleagues used amniotic fluid cells from pregnant women to help heal infants born with congenital heart defects. Amniotic fluids, drawn during standard tests, are generally discarded but show promise for implants made from a baby’s own genetically matched material.

“The main thing we’ve figured out is how to get a vascularized device: laboratory-grown tissue that is made entirely from amniotic fluid cells,” Jacot said. “We showed it’s possible to use only cells derived from amniotic fluid.”

Researchers from Rice, Texas Children’s Hospital and Baylor College of Medicine combined amniotic fluid stem cells with a hydrogel made from polyethylene glycol and fibrin. Fibrin is the proteins formed during blood clots, but it is also used for cellular-matrix interactions, wound healing and angiogenesis (the process by which new vessels are made). Fibrin is widely used as a bioscaffold but it suffers from low mechanical stiffness and is degraded rapidly in the body. When fibrin was combined with polyethylene glycol, the hydrogel became much more robust, according to Jacot.

Additionally, these groups used a growth factor called vascular endothelial growth factor to induce the stem cells to differentiate into endothelial cells. Furthermore, when induced in the presence of fibrin, these cells infiltrated the native vasculature from neighboring tissue to make additional blood vessels.

When mice were injected with fibrin-only hydrogels, thin fibril structures formed. However if those same hydrogels were infused with amniotic fluid stem cells that had been induced with vascular endothelial growth factor, the cell/fibrin hydrogel concoctions showed far more robust vasculature.

In similar experiments with hydrogels seeded with bone marrow-derived mesenchymal cells, once again, vascular growth was observed, but these vessels did not have the guarantee of a tissue match. Interestingly, seeding with endothelial cells didn’t work as well as the researchers expected, he said.

Jacot and others will continue to study the use of amniotic stem cells to build biocompatible patches for the hearts of infants born with birth defects and for other procedures.

Mesenchymal Stem Cells from Neonatal Thymus Helps Make New Blood Vessels


The thymus is an organ that sits over the top of the heart and it plays a pivotal role in the development of T-lymphocytes. The thymus is a very durable organ that can readily regenerate if it is injured. This regenerative ability is largely due to it high level of vascularization (lots of blood vessels). This vascularization is due to a robust population of resident mesenchymal stem cells that supports blood vessel formation in the damaged thymus. The process of blood vessel formation is called “angiogenesis.” The angiogenic potential of these thymus-based mesenchymal stem cells might hold excellent potential for regenerative therapies.

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As it turns out, neonatal surgeries tend to generate thymus tissue that is usually thrown out as medical waste. Ming-Sing Si from Mott’s Children Hospital in Ann Arbor, Michigan and colleagues isolated mesenchymal stem cells from these surgically-derived neonatal thymuses and tested their ability to stimulate blood vessels in an experimental setting.

Discarded thymus tissue was obtained from the University of Michigan, and this tissue was minced, degraded with enzymes, and cultured. The mesenchymal stem cells (MSCs) moved from the thymus tissue onto the culture dishes. These thymus-based MSCs grew like gangbusters in culture and could be passaged over 30 times.

Discarded human neonatal thymus tissue is a source of mesenchymal stromal cells (MSCs). (A): Discarded human neonatal thymus tissue during pediatric cardiac surgery. (B): Minced thymus tissue prior to plating. (C): Cells migrating from thymus tissue fragments during explant culture at 10 days. (D): Clonogenicity of thymus MSCs at 2 weeks (representative of 7 donors). (E): Colony-forming efficiency of thymus MSCs. (F): Averaged cumulative population doubling of thymus MSCs (n = 4) over 9 weeks of culture. Abbreviation: CFU-F, fibroblastic colony-forming unit.
Discarded human neonatal thymus tissue is a source of mesenchymal stromal cells (MSCs). (A): Discarded human neonatal thymus tissue during pediatric cardiac surgery. (B): Minced thymus tissue prior to plating. (C): Cells migrating from thymus tissue fragments during explant culture at 10 days. (D): Clonogenicity of thymus MSCs at 2 weeks (representative of 7 donors). (E): Colony-forming efficiency of thymus MSCs. (F): Averaged cumulative population doubling of thymus MSCs (n = 4) over 9 weeks of culture. Abbreviation: CFU-F, fibroblastic colony-forming unit.

When these thymus-based MSCs were combined with human umbilical vein endothelial cells, within one day, the cells formed an extensive network of blood vessels.

Thymus mesenchymal stromal cells (MSCs) cooperate with human umbilical vein endothelial cells (HUVECs) to form a network in a two-dimensional angiogenesis assay. (A): Monolayer appearance of HUVECs after 48 hours of culture on fibrin hydrogel. (B): Thymus MSCs clustered together after 24 hours of culture on fibrin hydrogel. (C): Combining HUVECs with thymus MSCs (2:1) resulted in the appearance of interconnected tubules at 24 hours. Scale bars = 100 μm. Results are representative of two independent experiments.
Thymus mesenchymal stromal cells (MSCs) cooperate with human umbilical vein endothelial cells (HUVECs) to form a network in a two-dimensional angiogenesis assay. (A): Monolayer appearance of HUVECs after 48 hours of culture on fibrin hydrogel. (B): Thymus MSCs clustered together after 24 hours of culture on fibrin hydrogel. (C): Combining HUVECs with thymus MSCs (2:1) resulted in the appearance of interconnected tubules at 24 hours. Scale bars = 100 μm. Results are representative of two independent experiments.

Gene expression studies showed that culturing thymus MSCs with human umbilical vein endothelial cells (HUVECs) caused the HUVECs to express a variety of blood vessel-specific genes.  These thymus-based MSCs were also able to induce blood vessels if the cells were wadded up into a ball (spheroids).

To top it all off, Si and others implanted thymus-based MSCs underneath the skin of nude mice.  They used hydrogels with no cells, hydrogels plus HUVECs, hydrogels plus thymus-based MSCs, and hydrogels with thymus-based MSCs plus HUVECs.  The control implants and the HUVEC implants showed no blood vessels.  HUVECs make very good blood vessels, but they have to be directed to do so.  Both the thymus-based MSCs and the MSCs plus HUVECs showed extensive integration into the host tissue with lots of blood vessels.

Thymus mesenchymal stromal cells (MSCs) incite angiogenesis in vivo. Fibrin constructs without spheroids (control) or with 500 spheroids with 600 human umbilical vein endothelial cells (HUVECs) per spheroid, 200 thymus MSCs per spheroid, or 600 HUVECs plus 200 thymus MSCs per spheroid were generated (n = 3 per group) and were implanted subcutaneously for 14 days in NOD-SCID mice. Explanted constructs were photographed (edges traced in A–D) and processed for histology. (A): Controls did not manifest local reaction. (B): HUVEC constructs appeared avascular. (C): Thymus MSC constructs were integrated and caused increased adjacent vascularization. (D): HUVEC plus thymus MSC constructs were integrated and surrounded by a host vascular response and appeared to have vessels within. (E–H): Construct hematoxylin and eosin staining. Scale bars = 50 μm. (E): Avascular tissue invasion of control construct. Scale bar = 100 μm. (F): HUVEC construct with adjacent cellularity and vascularity between panniculus carnosus muscle layer (∗) and construct. “Ghost” (†) of the prior locations of spheroid and necrotic spheroid (‡) were present in internal regions of all constructs with spheroids. (G): Thymus MSC construct with increased adjacent cellularity and vascularity. (H): HUVEC plus thymus MSC construct with increased vascularization within the construct. (I): Manual measurement of vessel density demonstrates significant differences by two-way analysis of variance. Control and HUVEC constructs had minimal adjacent vascularization. Thymus MSC constructs promoted the greatest adjacent response, whereas HUVEC plus thymus MSC constructs contained the greatest vessel density within the construct. (J, K): Immunohistochemical staining with human-specific CD31 monoclonal antibody revealed that only constructs with HUVEC plus thymus MSCs contained CD31-positive luminal structures with blood cells. Scale bar = 20 μm. Abbreviations: C, controls; H, human umbilical vein endothelial cell constructs; T, thymus mesenchymal stromal cell construct.
Thymus mesenchymal stromal cells (MSCs) incite angiogenesis in vivo. Fibrin constructs without spheroids (control) or with 500 spheroids with 600 human umbilical vein endothelial cells (HUVECs) per spheroid, 200 thymus MSCs per spheroid, or 600 HUVECs plus 200 thymus MSCs per spheroid were generated (n = 3 per group) and were implanted subcutaneously for 14 days in NOD-SCID mice. Explanted constructs were photographed (edges traced in A–D) and processed for histology. (A): Controls did not manifest local reaction. (B): HUVEC constructs appeared avascular. (C): Thymus MSC constructs were integrated and caused increased adjacent vascularization. (D): HUVEC plus thymus MSC constructs were integrated and surrounded by a host vascular response and appeared to have vessels within. (E–H): Construct hematoxylin and eosin staining. Scale bars = 50 μm. (E): Avascular tissue invasion of control construct. Scale bar = 100 μm. (F): HUVEC construct with adjacent cellularity and vascularity between panniculus carnosus muscle layer (∗) and construct. “Ghost” (†) of the prior locations of spheroid and necrotic spheroid (‡) were present in internal regions of all constructs with spheroids. (G): Thymus MSC construct with increased adjacent cellularity and vascularity. (H): HUVEC plus thymus MSC construct with increased vascularization within the construct. (I): Manual measurement of vessel density demonstrates significant differences by two-way analysis of variance. Control and HUVEC constructs had minimal adjacent vascularization. Thymus MSC constructs promoted the greatest adjacent response, whereas HUVEC plus thymus MSC constructs contained the greatest vessel density within the construct. (J, K): Immunohistochemical staining with human-specific CD31 monoclonal antibody revealed that only constructs with HUVEC plus thymus MSCs contained CD31-positive luminal structures with blood cells. Scale bar = 20 μm. Abbreviations: C, controls; H, human umbilical vein endothelial cell constructs; T, thymus mesenchymal stromal cell construct.

These MSCs show low expression of human leukocyte antigen class I, which, translated, means that these cells are unlikely to be recognized by the patient’s immune system.  Therefore, these cells could be donated to patients whose resident MSCs are of poor quality or do not have enough of their own MSCs for therapeutic processes.

This paper shows that discarded neonatal thymus contains large numbers of resident MSCs that can be isolated and cultured by a standard explant method.  These MSCs have all the characteristics of traditional MSCs, but have more robust growth characteristics in culture.  These thymus MSCs also possess outstanding proangiogenesis qualities that should be further tested and considered as promoters of tissue and organ regeneration in tissue engineering strategies.

Amniotic Fluid Stem Cells Aid Kidney Transplantation Success in a Pig Model


When a kidney patient receives a new kidney, the donated kidney undergoes a brief loss of blood supply followed by a restoration of the blood supply. This phenomenon is called ischemia/reperfusion (IR), and IR tends to cause cell death, followed by rather extensive scarring. Tissue scarring is called tissue fibrosis and a scarred kidney can lead to so-called transplant dysfunction, which means that the transplanted kidney does not work terrible well, and this can cause transplant failure.

Previous studies in laboratory rodents have shown that mesenchymal stem cells from amniotic fluid (afMSCs) are beneficial in protecting against transplant-induced fibrosis (Perin L, et al. PLoS One 2010;5:e9357; Hauser PV, et al. Am J Pathol 2010;177:2011-2021).

Now a research group at INSERM, France led by Thierry Hauet has developed a pig-based model of kidney autotransplantation that is comparable to the human situation with regards to the structure of the kidney and the damage that results from renal ischemia (for papers, see Jayle C, et al. Am J Physiol Renal Physiol 2007; 292: F1082-1093; and Rossard L, et al. Curr Mol Med 2012; 12: 502-505). On the strength of these previous experiments, Hauet’s group has published a new paper in Stem Cells Translational Medicine in which they report that porcine afMSCs can protect against IR-related kidney injuries in pigs.

Hauet and others showed that porcine afMSCs could be easily collected at birth and cultured. These cells showed the ability to differentiate into fat, and bone cells, made many of the same cell surface markers as other types of mesenchymal stem cells (e.g., CD90, CD73, CD44, and CD29), but showed a diminished ability to differentiate into blood vessel cells. When afMSCs are added to extirpated kidneys during the reperfusion (reoxygenation) process in an “in vitro” (fancy way of saying “in a culture dish”) model of organ-preservation, these stem cells significantly increased the survival of blood vessel (endothelial) cells. Endothelial cells are one of the main targets of ischemic injury, and the added cells bucked up these endothelial cells and rescued them from programmed cell death. In addition to these successes, Hauet and others showed that adding intact porcine afMSCs was not necessary, since addition of the culture medium used to grow the afMSCs (conditioned medium or CM) also rescued kidney endothelial cell death. The afMSC-treated kidneys survived because they had significantly larger numbers of blood vessels, and this seems to be the main factor that causes the extirpated kidney to survive intact.

While these experiments were successful, Hauet and others know that unless they were able to show that these cells improved kidney transplant outcomes in a living animal, their research would not be deemed clinically relevant. Therefore, Hauet and others injected afMSCs into the renal artery of pigs that had received a kidney transplant six days after the transplant. IR injuries following kidney transplants led to increased serum creatinine levels, but those pigs that had been infused with afMSCs showed reduced creatinine levels and lower protein levels in their urine (proteinuria). In fact, seven days after the stem cell infusion, the urine creatinine and protein levels had returned to pre-transplant levels. Three months after the transplant, the pigs were put down, and then the kidneys were subjected to tissue analyses. Microscopic examination of tissue slices from these kidneys showed that afMSC injection preserved the structural integrity of microscopic details of the kidneys and reduced the signs of inflammation. Control animals that were not treated with afMSCs showed disruption of the microscopic structures of the kidneys and extensive inflammation and scarring. Also, because the kidney controls blood chemistry, a comparison of the blood chemistries of these two groups of animals showed that the blood chemistries of the afMSC-treated animals were normal as opposed to the control animals.

Amniotic Fluid Stem Cells Aid Kidney Transplantation in Porcine Model

Molecular analyses also showed a whole host of pro-blood vessel molecules in the kidneys of the afMSC-treated pigs. VEGFA (pro-angiogenic growth factor), and Ang1 (capillary structure strengthening and maintenance of vessel stability), proteins were increased in the kidneys of afMSC animals compared to control animals. Thus the infused stem cells increased the expression of pro-blood vessel molecules, which led to the formation of larger quantities of blood vessels, reduced cell death and decreased inflammation.

These findings demonstrate the beneficial effects of infused afMSCs on kidney transplant. Since afMSCs are easy to isolate and grow in culture, secrete proangiogenic and growth factors, and can differentiate into many cell lineages, including renal cells (see Perin L, et al. Cell Prolif 2007; 40: 936-948; De Coppi P, et al. Nat Biotechnol 2007; 25: 100-106; and In ‘t Anker PS, et al. Stem Cells 2004;22:1338-1345). This makes these cells a viable candidate for clinical application. This study also highlights pigs as a preclinical model as a powerful tool in the assessment of stem cell-based therapies in organ transplantation.

Umbilical Cord Stem Cells Preserve Heart Function After a Heart Attack in Mice


A consortium of Portuguese scientists have conducted an extensive examination of the effects of mesenchymal stromal cells from umbilical cord on the heart of mice that have suffered a massive heart attack. Even more remarkable is that these workers used a proprietary technique to harvest, process, and prepare the umbilical cord stem cells in the hopes that this technique would give rise to a commercial product that will be tested in human clinical trials,

Human umbilical cord tissue-derived Mesenchymal Stromal Cells (MSCs) were obtained by means of a proprietary technology that was developed by a biomedical company called ECBio. Their product,, UCX®, consists of clean, high-quality, umbilical cord stem cells that are collected under Good Manufacturing Practices. The use of Good Manufacturing Practice means that UCX is potentially a clinical-grade product. Thus, this paper represents a preclinical evaluation of UCX.

This experiments in this paper used standard methods to give mice heart attacks that were later received injections of UCX into their heart muscle. The same UCX cells were used in experiments with cultured cells to determine their effects under more controlled conditions.

The mice that received the UCX injections into their heart muscles after suffering from a large heart attack showed preservation of heart function. Also, measurements of the numbers of dead cells in the heart muscle of heart-sick mice that did and did not receive injections of umbilical cord cells into their hearts showed that the umbilical cord stem cells preserved heart muscle cells and prevented them from dying. Additionally, the implanted umbilical cord MSCs induced the growth and formation of many small blood vessels in the infarcted area of the heart. This prevented the heart from undergoing remodeling (enlargement), and preserved heart structure and function.

When subjected to a battery of tests on cultured cells, UCX activated cardiac stem cells, which are the resident stem cell population in the heart. Implanted UCX cells activated the proliferation of cardiac stem cells and their differentiation into heart muscle cells. There was no evidence that umbilical cord MSCs differentiated into heart muscle cells and engrafted into the heart. Rather UCX seems to help the heart by means of paracrine mechanisms, which simply means that they secrete healing molecules in the heart and help the heart heal itself.

In conclusion, Diana Santos Nascimento, the lead author of this work, and her colleagues state that, “the method of UCX® extraction and subsequent processing has been recently adapted to advanced therapy medicinal product (ATMP) standards, as defined by the guideline on the minimum quality data for certification of ATMP. Given that our work constitutes a proof-of-principle for the cardioprotective effects UCX® exert in the context of MI, a future clinical usage of this off-the-shelf cellular product can be envisaged.”

Preclinical trials with larger animals should come next, and after that, hopefully, the first human clinical trials will begin.

Nanotubules Link Damaged Heart Cells With Mesenchymal Stem Cells to Both of Their Benefit


Mesenchymal stem cells are found throughout the body in bone marrow, fat, tendons, muscle, skin, umbilical cord, and many other tissues. These cells have the capacity to readily differentiate into bone, fat, and cartilage, and can also form smooth muscles under particular conditions.

Several animal studies and clinical trials have demonstrated that mesenchymal stem cells can help heal the heart after a heart attack. Mesenchymal stem cells (MSCs) tend to help the heart by secreting a variety of particular molecules that stimulate heart muscle survival, proliferation, and healing.

Given these mechanisms of healing, is there a better way to get these healing molecules to the heart muscle cells?

A research group from INSERM in Creteil, France has examined the use of tunneling nanotubes to connect MSCs with heart muscle cells. These experiments have revealed something remarkable about MSCs.

Florence Figeac and her colleagues in the laboratory of Ann-Marie Rodriguez used a culture system that grew fat-derived MSCs and with mouse heart muscle cells. They induced damage in the heart muscle cells and then used tunneling nanotubes to connect the fat-based MSCs.

They discovered two things. First of all, the MSCs secreted a variety of healing molecules regardless of their culture situation. However, when the MSCs were co-cultured with damaged heart muscle cells with tunneling nanotubes, the secretion of healing molecules increased. The tunneling nanotubes somehow passed signals from the damaged heart muscle cells to the MSCs and these signals jacked up secretion of healing molecules by the MSCs.

The authors referred to this as “crosstalk” between the fat-derived MSCs and heart muscle cells through the tunneling nanotubes and it altered the secretion of heart protective soluble factors (e.g., VEGF, HGF, SDF-1α, and MCP-3). The increased secretion of these molecules also maximized the ability of these stem cells to promote the growth and formation of new blood vessels and recruit bone marrow stem cells.

After these experiments in cell culture, Figeac and her colleagues used these cells in a living animal. They discovered that the fat-based MSCs did a better job at healing the heart if they were previously co-cultured with heart muscle cells.

Exposure of the MSCs to damaged heart muscle cells jacked up the expression of healing molecules, and therefore, these previous exposures made these MSCs better at healing hearts in comparison to naive MSCs that were not previously exposed to damaged heart muscle.

Thus, these experiments show that crosstalk between MSCs and heart muscle cells, mediated by nanotubes, can optimize heart-based stem cells therapies.

The Therapeutic Potential of Fat-Based Stem Cells Decreases With Age


Fat is a rich source of stem cells for regenerative medicine.  Treating someone with their own stem cells from their own fat certainly sounds like an attractive option.  However, a new study shows that demonstrates that the therapeutic value of fat-based stem cells declines when those cells come from older patients.

“This could restrict the effectiveness of autologous cell therapy using fat, or adipose-derived mesenchymal stromal cells (ADSCs), and require that we test cell material before use and develop ways to pretreat ADSCs from aged patients to enhance their therapeutic potential,” said Anastasia Efimenko, M.D., Ph.D.  Dr Efimenko and Nina Dzhoyashvili, M.D., were first authors of the study, which was led by Yelena Parfyonova, M.D., D.Sc., at Lomonosov Moscow State University, Moscow.

Heart disease remains the most common cause of death in most countries.  Mesenchymal stromal cells (MSCs) collected from either bone marrow or fat are considered one of the most promising therapeutic agents for regenerating damaged tissue because of their ability to proliferate in culture and differentiate into different cell types.  Even more importantly they also have the ability to stimulate the growth of new blood vessels (angiogenesis).

In particular, fat is considered an ideal source for MSCs because it is largely dispensable and the stem cells are easily accessible in large amounts with a minimally invasive procedure.  ADSCs have been used in several clinical trials looking at cell therapy for heart conditions, but most of the studies used stem cells from relatively healthy young donors rather than sick, older ones, which are the typical patients who suffer from heart disease.

“We knew that aging and disease itself may negatively affect MSC activities,” Dr. Dzhoyashvili said. “So the aim of our study was to investigate how patient age affects the properties of ADSCs, with special emphasis on their ability to stimulate angiogenesis.”

The Russian team analyzed age-associated changes in ADSCs collected from patients of different age groups, including some patients who suffered from coronary artery disease and some without.  The results showed that ADSCs from the older patients in both groups showed some of the characteristics of aging, including shorter telomeres (the caps on the ends of chromosomes that protect them from deterioration), which confirms that ADSCs do age.

“We showed that ADSCs from older patients both with and without coronary artery disease produced significantly less amounts of angiogenesis-stimulating factors compared with the younger patients in the study and their angiogenic capabilities lessened,” Dr. Efimenko concluded. “The results provide new insight into molecular mechanisms underlying the age-related decline of stem cells’ therapeutic potential.”

“These findings are significant because the successful development of cell therapies depends on a thorough understanding of how age may affect the regenerative potential of autologous cells,” said Anthony Atala, M.D., director of the Wake Forest Institute for Regenerative Medicine, and editor of STEM CELLS Translational Medicine, where this research was published.