Induced Pluripotent Stem Cells Repair Spinal Cord Injury in Mice


Induced pluripotent stem cells (iPSCs), are made from adult cells by means of genetic engineering and share many, though not all, of the characteristics of embryonic stem cells. The regenerative capacity of iPSCs is truly remarkable, but there are definitely safety concerns with them. The procedure that makes iPSCs from adult cells drives them to divide quickly and often. These cell divisions produce high rates of genetic mutations, some of which are of little consequence, and others that are. Also prolonged culture of iPSCs can select for cells that acquire cancer-causing mutations. Laboratory tests have established that iPSCs have a capability to cause tumors in laboratory animals that at least equals that of embryonic stem cells.

Nevertheless, some labs have designed protocols to screen iPSC lines for tumor-causing or non-tumor-causing lines. Also, iPSCs have been successfully used in therapeutic experiments in laboratory animals without generating tumors. Therefore, iPSCs might be closer to therapeutic use than we think.

With this comes a fascinating publication from the Laboratory of Molecular Neuroscience in the Graduate School of Biological Sciences at the Nara Institute of Science and Technology in Ikoma, Japan; specifically from the laboratory of Kinichi Nakashima. In this experiment, workers in Nakashima’s laboratory used iPSCs that were made from mouse adult cells to make neural stem cells (NSCs).

NSCs are found in the central nervous system and they replace cells in the central nervous system or augment the central nervous system in response to learning and memory or things like that. NSCs are not a monolithic cell population, since some NSCs have the ability to make specific populations of neurons (the cells responsible for neural impulses), while others form glial cells (the cells that support and maintain the neurons).

Nakashima’s laboratory has designed a highly efficient protocol for converting iPSCs into NSCs. They predicted that these NSCs would represent a much less mixed population. Nakashima surmised that such NSCs would almost certainly do a better job of repairing a spinal cord injury. Therefore, led by Yusuke Fujimoto, his colleagues produced several iPSC lines and converted them into NSCs. They called these cell lines “neuroepithelial-like stem cells from human iPS cells” or hiPS-lt-NES cells.

Characterization of these cells in culture showed that they were a homogeneous population that differentiated into many different types of spinal-specific neurons and glial cells. Next, as predicted by Nakashima, Fujimoto and his colleagues transplanted these hiPS-lt-NES cells into the spinal cords of mice that had suffered spinal cord injuries.

The results were remarkable. The transplanted hiPS-lt-NES cells differentiated into neural cells in the spinal cord and promoted functional recovery of hind limb motor function. This is a remarkable finding, but perhaps the transplanted cells only secreted growth factors that helped heal the spine and played no real role in regenerating the spinal cord. Nakashima was not satisfied with this result.

To determine if the transplanted cells were actually regenerating the spinal cord, Fujimoto and the rest of his laboratory workers used two different tracers and also killed off the transplanted cells. The nerve cell tracers showed that the transplanted cells and nerve cells that were already in the spinal cord formed the new neural networks and connections to restore normal hind limb function. Neurons native to the spinal cord and the newly introduced neurons hat were formed from transplanted hiPS-lt-NES cells reconstructed the corticospinal tract by forming proper connections with other neurons and integrating neuronal circuits. Then, when they deliberately killed off the transplanted cells, no neural regeneration occurred. Thus the transplanted hiPS-lt-NES cells not only contributed to the regeneration of the spinal cord and its neural circuits, but they initiated and drove the process.

These fascinating findings suggest a new way to treat spinal cord injury and it does not require the killing of embryos.

The FOCUS-CCTRN Trial – Transendocardial Delivery of Bone Marrow Stem Cells Improves Heart Function in Heart Attack Patients


Mayo Clinic researchers have completes a Phase II clinical study that demonstrates that bone marrow stem cells can fix a sick heart. They discovered that stem cells derived the bone marrow of heart patients, when isolated and injected into their hearts, improved heart function. These researchers also found that particular types of the stem cells seemed to be responsible for the largest patient improvement, and, therefore, warrant further study.

This clinical study is an extension of earlier work in Brazil that treated a small number of patients with fewer stem cells (Perin EC, Dohmann HF, Borojevic R, et al. Transendocardial, autologous bone marrow cell transplantation for severe, chronic ischemic heart failure. Circulation. 2003;107(18):2294-2302.). The earlier study treated 21 patients, seven of whom received placebo treatments and fourteen others who received injections of bone marrow stem cells into the walls of their hearts.  In this study, a total of 92 (82 men; average age: 63 years) were randomly assigned to the placebo or experimental groups (n=61 in Bone Marrow Cell transplant group and n=31 in the placebo group).  This patient group suffered from coronary artery disease or LV dysfunction, and limiting heart failure or angina.  These patients had weakened hearts as a result of previous heart attacks.

These 92 patients received either a placebo (sterile saline bereft of any cells) or 100 million bone marrow-derived stem cells that were extracted from the patient’s hips. In all cases the treatment consisted of a one-time injection into the wall of the heart.  This injection procedure actually consisted of 15 small injections in stem cells into regions of the ventricle wall that were known to consist of live cells as demonstrated by previous “electromechanical mapping” studies of the heart (see Willerson JT, Perin EC, Ellis SG, et al. Intramyocardial injection of autologous bone marrow mononuclear
cells for patients with chronic ischemic heart disease and left ventricular dysfunction (First Mononuclear Cells injected in the US [FOCUS]). Am Heart J. 2010;160(2):215-223
for a description of this mapping).  The injections were made performed with a NOGA catheter.  This clinical trial is the first clinical to use such a large a dose of stem cells.

NOGA Catheter

The significance of using these patient’s own bone marrow stem cells is not lost on cardiologists, since previous reports have shown that bone marrow from patients with chronic heart conditions or who have suffered heart attacks show diminished stem cell populations and activities (see Heeschen C, Lehmann R, Honold J, et al. Profoundly reduced neovascularization capacity of bone marrow mononuclear cells derived from patients with chronic ischemic heart disease. Circulation. 2004;109(13):1615-1622 & Kissel CK, Lehmann R, Assmus B, et al. Selective functional exhaustion of hematopoietic progenitor cells in the bone marrow of patients with postinfarction heart failure. J Am Coll Cardiol. 2007;49(24):2341-2349).  If higher doses of stem cells can still help improve the function of such heart patients, then perhaps such a protocol would be helpful for them.

Mayo Clinic cardiologist Robert Simari, who was part of this study, said “We found that the bone marrow cells did not have a significant impact on the original end points that we chose, which involved reversibility of a lack of blood supply to the heart, the volume of the left ventricle of the heart at the end of a contraction, and maximal oxygen consumption derived through a treadmill test.” Simari is chairman of the Cardiovascular Cell Therapy Research Network (CCTRN), which is a network of five academic centers and associated satellite sites that conducted the study. The CCTRN is supported by the National Heart, Lung, and Blood Institute, which also funded the study.

Simari described the results of this study: “But interestingly, we did find that the very simple measure of ejection fraction was improved in the group that received the cells compared to the placebo group by 2.7 percent.” Ejection fraction refers to the average percentage of blood pumped from the left ventricle each time the heart pumps.  You can listen to Simari discuss this clinical trial here.

Emerson Perin, and James Willerson of the Texas Heart Institute, who were the principal investigators in this study, noted that although 2.7 percent does not seem like a large number, it does represent a statistically significant increase and this means an improvement in heart function for chronic heart failure patients who have no other options.

Dr. Perin noted, “This was a pretty sick population. They had already had heart attacks, undergone bypass surgery, and had stents placed. However, they weren’t at the level of needing a heart transplant yet. In some patients, particularly those who were younger or whose bone marrows were enriched in certain stem cell populations had even greater improvements in their ejection fractions.”

The study participants had an average age of 63 years old, but this study showed that those patients who are younger than the average participant age improved more than the average. In these patients, the ejection fraction improved by 4.7 percent. The variable that seemed to predict whether or not the patient would benefit from this procedure was the quality of their bone marrow stem cells.  Detailed examinations of bone marrow stem cell populations from each patient showed that younger patients who showed greater improvements have large quantities of CD34+- and CD133+-type stem cells in their bone marrow isolates.  Stem cells with these particular markers tend to produce blood vessels and making more blood vessels, increases the flow of oxygen and nutrients to the heart muscle.  This spares the damaged heart muscle from experiencing more damage and shores the existing heart muscle to improve its function.

Dr. Simari concluded, “This tells us that the approach we used to deliver the stems cells was safe. It also suggests new directions for the next series of clinical trials, including the type of patients, endpoints to study and types of cells to deliver.”

Dick Cheney’s Heart Transplant


Because people have asked me to comment on the Dick Cheney heart transplant, I thought I would make one entry about it. Readers of this blog will recognize that I have very conservative leanings when it comes to subjects such as politics and health care. Also, the organ transplant waiting lists are local and federal. The decision to put someone on the organ recipient list is a decision that is between the patient and their physicians. I do not think the government has any right to intercede in the decision because it is a private decision. The shortage of organs can be addressed in other ways, but it seems to me that rationing by the government is simply wrong and contrary to the founding principles of our constitutional republic.

Having said all that, Cheney waited 20 months to receive his heart, and he was given no special treatment. You can argue that a younger person should have received this heart, but why? Cheney waited his turn. His age was, in his doctor’s opinion, not an important factor. Therefore, we should go with his doctor and not some bureaucrat.

Nevertheless, the best story on this comes from the inimitable Wesley Smith.  Read his view here.  It says it all.

GABA-Making Neurons Made from Stem Cells Reverse Motor Defects in Mice with a Form of Huntington’s Disease


Huntington disease is a horrible, slow, relentless and progressive death sentence. This disease is inherited, and if one of your parents has Huntington’s disease (HD), you have a 50% chance of inheriting the disease. HD is cause by mutations in a gene found on human chromosome 4. This mutation resides in a gene that encodes the Huntingtin protein. However, these mutations are unusual in that they are due to excessive number of repeats of the triplet sequence, CAG. CAG codes for the amino acid glutamine, and normally, there is a stretch of 10-28 glutamines in normal versions of the Huntingtin protein. However, CAG repeats tend to cause the enzymes that make DNA to slip and resynthesize the repeat, thus causing the number of consecutive CAG triplets in this gene to expand. In persons with Huntington’s disease, the CAG triplet is repeated anyways from 36 to 120 times. This expands the stretch of glutamine residues and creates and toxic protein that is cut into smaller fragments that kill nerve cells.

The symptoms of Huntington’s disease usually begin with behavioral disturbances that show up before the onset of movement disorders. These behavioral symptoms can include hallucinations, irritability, moodiness, restlessness or fidgeting, paranoia, and even psychosis. Abnormal movements begin and these include facial movements, including grimaces, the turning of the head to shift eye position rather than moving the eyes, quick, sudden, sometimes wild jerking movements of the arms, legs, face, and other body parts, slow, uncontrolled movements, and an unsteady gait. The dementia slowly gets worse and other symptoms eventually emerge that include disorientation or confusion, loss of judgment, loss of memory, personality changes, and speech changes.

This disease has no treatments and no cure, but researchers have published a paper in the journal Cell Stem Cell that is a starting block of further research that might lead to a treatment. In this paper, a special type of brain cell generated from stem cells seems to help ameliorate the muscle coordination deficits that eventually lead to uncontrollable spasms (choreas) that are so characteristic of the disease.

Su-Chun Zhang, a neuroscientist at the University of Wisconsin-Madison and senior author of the new study said: “This is really something unexpected.” This work suggests that locomotion could be restored in mice with a Huntington’s-like condition.

Zhang’s laboratory has a great deal of experience and expertise at making different types of brain cells from human embryonic stem cells or induced pluripotent stem cells. In the newly published article, Zhang and his colleagues reported the production of neurons that use a neurotransmitter called “gamma-amino butyric acid,” which thankfully goes by the acronym “GABA.” GABA is one of the most heavily used neurotransmitters in the central nervous system, and GABA receptors come in many shapes and sizes, but virtually all of them are chloride channels. While this may not mean anything to you, to a neuron that is trying to generate a nerve impulse, chloride ions are inhibitory and they cut the neuron off at the knees. GABA, therefore, is an extremely important inhibitory neurotransmitter that shuts neurons down when they need to be shut down.

This significance of making GABA-using neurons in the laboratory cannot be lost on Huntington’s patients, because GABA-making neurons are the ones that take the biggest beating during the onset of Huntington’s disease. Without these GABA-using neurons, it is impossible for various portions of the brain to properly coordinate movement. According to Zhang, GABA-producing neurons produce one the key neurotransmitters for coordinating movement.

At the UW-Madison Waisman Center, Zhang and his colleagues discovered how to make large quantities of GABA neurons from human embryonic stem cells. They then tested these neurons in mice that had an induced condition that resembled Huntington’s disease. They implanted these cells in the brains of mice, and they were very surprised to see that the implanted cells not only integrated into the brain, but also projected axons to the correct targets and effectively reestablished the broken communication network. This largely restored motor function.

Zhang noted that these results surprised so because GABA-making neurons are found in a part of the brain called the basal ganglia. The basal ganglia play a central role in voluntary motor coordination. However, GABA-making neurons, however, exert their influence at a distance on cells in the midbrain through neural circuits that are fueled by the GABA-making neurons.

Zhang explained it this way: “This circuitry is essential for motor coordination, and it is what is broken in Huntington patients. The GABA neurons exert their influence at a distance through this circuit. Their cell targets are far away.”

Zhang, however, did not stop there. Many neuroscientists do not think that the results Zhang and his co-workers observed are even possible. He explained further: “Many in the field feel that successful cell transplants would be impossible because it would require rebuilding the circuitry. But what we’ve shown is that the GABA neurons can remake the circuitry and produce the right neurotransmitter.”

This new study has profound implications for regenerative therapy of neurodegenerative disease. One day, it might be possible to treat Huntington’s disease with cell transplants that capitalize on the plasticity of the adult brain. Zhang noted that the adult brain is considered by some neuroscientists to be stable and not easily susceptible to therapies that try to correct things like broken neural circuits. For a therapy to work, it has to be engineered so that it targets only specific cells. Zhang added, “The brain is wired in such a precise way that if a neuron projects the wrong way, it could be chaotic.”

This new research is indeed promising, but it must be worked up and correlated from the mouse model to the condition found in human patients, and this type of very hard, tedious work will take a great deal of time, people hours, and a whole lot of trial and error. However, for a disease that now has no effective treatment, this work could become the next best hope for Huntington’s disease patients.

A caveat to this research is that the mice with Huntington’s disease-like symptoms were given the disease by means of the chemical called quinolinic acid. Administration of this chemical by means of “bilateral intrastriatal microinjections,” which is a fancy way of saying injecting really small amounts of this stuff into a specific part of the basal ganglia, generates mice that display the movement disorders similar to those seen in humans with this disease (see Sanberg PR, et al., Experimental Neurology 1989 Jul;105(1):45-53). Also, the pathology of the brains of these mice shows some similarity to that observed postmortem in the brains of Huntington’s disease patients.

The problem is this: implanting cells into the brains of mice that have been subjected to quinolinic acid results in those cells living and taking up residence in the brain of the mouse and somewhat reconstructing the striatum of the mouse brain (see Dunnett SB. Novartis Found Symp. 2000;231:21-41; discussion 41-52). This is due to the fact that quinolinic acid lesions in the brain specifically kill off particular parts of the brain, but the environment of the brain is still relatively normal. When similar experiments are attempted in human patients, the implanted tissue takes a beating and dies because the brains of Huntington’s disease patients are not chemically altered, but genetically altered. These brains are a toxic waste dump, so to speak, and implanted tissue or cells die (see Francesca Cicchetti, Denis Soulet, and Thomas B. Freeman. “Neuronal degeneration in striatal transplants and Huntington’s disease: potential mechanisms and clinical implications,” Brain (2011) 134 (3): 641-652. doi: 10.1093/brain/awq328).

It seems to me that the environment of the brain must be improved before cell therapy is going to work, and that is a much more difficult problem to address. Dying neurons spill their neurotransmitters into the intracellular space. Huge neurotransmitter overdose can kill nearby neurons and this contributes to the toxic environment in the brain of Huntington’s disease patients. Finding a way to quell the poisonous products released by dead neurons is the next great unanswered quest for these patients.

SanBio Tests Its Mesenchymal Stem Cell Line SB623 as a Treatment for Strokes


California-based biotechnology company, SanBio Inc., has announced the successful enrollment of its first patients in a Phase 1/2a clinical trial that will test the safety and efficacy of a novel stem cells product in the treatment of chronic deficits that are the product of strokes. This stem cell product is called SB623, and so far, 6 of 18 patients have been given this product. This clinical trial is being conducted at the University of Pittsburgh and Stanford University. The trial is being conducted at Stanford University and the University of Pittsburgh. Thus far, no safety concerns have been reported.

SB623 is a stem cell line that was originally derived from adult bone marrow stem cells. Specifically, mesenchymal stem cells were isolated from bone marrow and cultured. They were then genetically engineered to express a modified version of the “Notch” gene. The Notch gene encodes a protein that is embedded into the membrane and has regions that extend to the cell exterior and another portion that extends to the cell interior. The scientists who made SB623 forced the mesenchymal stem cells to express the internal portion of the Notch protein. The significance of this is simple; the internal portion of the Notch protein does all the work and the external portion of it regulates the internal portion. By expressing only the internal portion of the Notch protein, the scientists made a version of the Notch protein that is always active. When active, the Notch protein turns mesenchymal stem cells into cells that support neurons, which are the main functional cells of the nervous system that transmit neural impulses.  Therefore, SB623 cells are derivatives of mesenchymal stem cells that have the capacity to form neurons or cells that greatly resemble neurons.

SanBio scientists and others have used SB623 cells in laboratory rodents that have sufered strokes. In all animal studies, SB623 cells appear to be safe and efficacious. Tate and colleagues published a paper in the journal Cell Transplantation in 2010 entitled, “Human mesenchymal stromal cells and their derivative, SB623 cells, rescue neural cells via trophic support following in vitro ischemia.” This paper (Cell Transplant. 2010;19(8):973-84), SB623 cells were co-cultured with brain slices after those slices had been deprived of oxygen, which is exactly what happens to the brain during a stroke. SB623 cells or the medium that was used to grow SB623 cells rescued cells in the brain slices from dying. This effect was also dosage dependent.

In an earlier paper, SanBio scientists showed that SB623 cells made scaffolds of molecules that supported the growth of neurons (Aizman et al., J Neurosci Res. 2009 Nov 1;87(14):3198-206). In other work, scientists at Northwestern University implanted SB623 cells into the brains of rats with Parkinson’s disease and showed that they prevented the death of dopaminergic neurons; the cells that usually die during Parkinson’s disease (Glavaski-Joksimovic A,, et al., Cell Transplant. 2009;18(7):801-14). Therefore, the use of SB623 cells in rodents points to a potential for these cells as therapeutic agents in human disease.

The Chief Executive Officer for SanBio, Keita Mori, said of this trial, “This represents a major milestone in the human clinical testing of this important new approach for regenerative medicine. We are pleased to learn that the initial dose level was well tolerated.” In this clinical trial, SB623 is implanted into the damaged region of the brains of stroke patients. Product safety is the primary focus of the study; however, particular tests and measurements of efficacy are also being tested.

SanBio’s Vice President of Development, Ernest Yankee said, “The successful completion of the initial dose cohort is a major step in any first-in-human study. We are looking forward to initiating the next two dose cohorts and wrapping up the study. The safety findings thus far are very encouraging”

Neuronal Stem Cells Made from Mature Skin Cells


Stem cell researcher Hans Schöler and his colleagues at the Max Planck Institute for Molecular Biomedicine in Münster, Germany, have successfully isolated neural stem cells from completely differentiated skin cells. Workers and Schöler’s lab procured skin cells from mice and exposed them to a cocktail of special proteins called “growth factors,” and concurrently subjected them to specific culture conditions. This induced the skin cells to differentiate into neuronal somatic stem cells. Schöler noted that their research “shows that reprogramming somatic cells does not require passing through a pluripotent stage.” These new approaches to regenerative medicine can produce stem cells in a shorter time period and are also safer for human clinical use.

Pluripotent stem cells have definitely been the darling of stem cell science since their discovery. When exposed to the right environment, pluripotent stem cells differentiate into every type of cell in the body. However, the pluripotency of these cells, while being their grace is also their curse. According to Schöler, “pluripotent stem cells exhibit such a high degree of plasticity that under the wrong circumstances they may form tumors instead of regenerating a tissue or an organ.” However reprogrammed stem cells can provide a way around these dangers, since they are not pluripotent, but Multipotent (they can only give rise to select subset of cell types rather than any cell type). This can give them an edge in terms of safety and therapeutic potential.

To convert skin cells into stem cells, the Max Planck researchers invented an ingenious protocol that combined several different growth factors (proteins that direct cellular growth) in a culture system that grows the cells and encourages their differentiation into stem cells. One of these growth factors is called Brn4, and Brn4 had never been used in reprogramming experiments before. However, Schöler’s group discovered that Brn4 is one of the most powerful inducers of the stem cell fate in skin cells. The reprogramming of mature skin cells into neuronal stem cells is even more effective if the growth factor-treated skin cells are grown in specific culture conditions. Such culture conditions drive the cells to divide faster and, according to Schöler, the cells gradually “lose their molecular memory that they were once skin cells.” Only after a few cell divisions, the newly produced neuronal somatic stem cells are, for the most part, indistinguishable from neuronal stem cells extracted from neural tissue.

There are other reasons that this work from Schöler’s laboratory might be readily applicable to clinical settings. According the Schöler, “The fact that these cells are multipotent dramatically reduces the risk of neoplasm formation, which means that in the not-too-distant future they could be used to regenerate tissues damaged or destroyed by disease or old age; until we get to that point, substantial research efforts will have to be made.” However, these experiments were done with mouse skin cells. In order to show that this protocol could work for human regenerative medicine, Schöler and his colleagues must demonstrate that human skins cells can also undergo a similar transformation. Additionally, it is crucial to show that these skin cell-derived neuronal stem cells are stable over long periods of time in culture and when implanted into laboratory animals.

Schöler concluded with these remarks: “Our discoveries are a testament to the unparalleled degree of rigor of research conducted here at the Münster Institute. We should realize that this is our chance to be instrumental in helping shape the future of medicine.” At this point, the project is still in its initial, basic science stage although “through systematic, continued development in close collaboration with the pharmaceutical industry, the transition from the basic to the applied sciences could be hugely successful, for this as well as for other, related, future projects. The blueprints for this framework are all prepped and ready to go – all we need now are for the right political measures to be ratified to pave the way towards medical applicability.”

Fat-Derived Mesenchymal Stem Cells Aid Wound Healing


Breaches in the skin produce wounds that have the ability to heal, but take time to do so. During the time prior to healing, the wound is subject to irritation, pain, and infection. Speeding up wound healing is a necessary to prevent wound infections and other wound-related morbidities.

Wound healing requires a somewhat complicated chain of events that includes interactions with nearby cells and tissues. Wound healing is slower in patients with conditions such as type 1 diabetes mellitis. New therapeutic methods are available for chronic wounds, but there are no satisfactory methods for treating chronic wounds that stubbornly refuse to heal.

Stem cell treatments have been tested as potential treatments for chronic wounds. Mesenchymal stem cells (MSCs) from bone marrow can accelerate wound healing in a rodent model system (see Wu Y, et al., “Mesenchymal stem cells enhance wound healing through differentiation and angiogenesis. Stem Cells 2007;25:2648-2659, & Chen L, et al., “Paracrine factors of mesenchymal stem cells recruit macrophages and endothelial lineage cells and enhance wound healing.” PLoS One 2008;3:e1886). However, the acquisition of a patient’s bone marrow MSCs requires bone marrow aspirations, and if a patient already has a chronic wound that refuses to heal, introducing anther lesion is probably not a good idea.

Therefore, a South Korean research group as tried to use fat-based MSCs, or adipose tissue-derived MSCs (ADSCs) to accelerate wound healing in a rodent model system. The paper reference is Seung Ho Lee, et al., “Effects of Human Adipose-derived Stem Cells on Cutaneous Wound Healing in Nude Mice,” Ann Dermatol Vol. 23, No. 2, 2011 DOI: 10.5021/ad.2011.23.2.150, and it can be found at this link.

In this work, Lee and his team counted on earlier work that showed that ADSCs improved wound healing in mice that suffered from an inherited form of type 2 diabetes mellitis (Nambu M, et al., “Accelerated wound healing in healing-impaired db/db mice by autologous adipose tissue-derived stromal cells combined with atelocollagen matrix,” Ann Plast Surg 2009;62:317-321.). In other experiments, human ADSCs accelerated the closure of wounds in nude mice (Kim WS, et al., “Wound healing effect of adipose-derived stem cells: a critical role of secretory factors on human dermal fibroblasts,” J Dermatol Sci 2007;48:15-24). Nude mice have a mutation in the FOXN1 gene, which causes them to be born without a thymus gland or body fur. The lack of a thymus gland means that they do not have T cells and this makes them unable to reject tissues that are transplanted into them.

In this study Lee and his colleagues determined the benefits of human ADSCs in wound healing on a nude mice. They used a contraction-preventing splint method, and covered each wound with either ADSC-populated collagen gels (CG), human dermal fibroblast (DFs)-populated CG, or CG alone. They measured the size and thickness of the wounds after healing, and examined the histology of the wounds once they had healed.

The results were rather clear. Wound sizes after ASC treatment was significantly smaller than those wounds that were treated with CG alone (28.63±5.05 mm2, 54.63±5.69 mm2, p<0.05). Wounds treated with DFs healed significantly faster than wounds treated with either ASCs and CG alone (11.09±2.71 mm2, p<0.05). However, when the healed tissue was excised and examined under the microscope, the dermal portion of ASCs-treated wounds was thicker than the others, but the DF-treated wounds was thicker than those treated with CG alone (84.50±4.39μm, 75.78±4.52μm, 51.61±2.31μm, p<0.05).

Dermal fibroblasts (DFs) accelerated wounds faster than ADSCs.   Several reports in the literature have shown that DFs can accelerate cutaneous wound healing.  When seeded in a collagen sponge matrix, DFs facilitated dermal and epidermal wound healing better than wounds treated with the collagen sponge only.  Skin substitutes with dermal components that contain DFs induce the proliferation and differentiation of skin cells (keratinocytes) and increase formation of basement membrane.  Both of these accelerate wound re-epithelialization (Okamoto E, Kitano Y. Expression of basement membrane components in skin equivalents–influence of dermal fibroblasts. J Dermatol Sci 1993;5:81-88; Maruguchi T, Maruguchi Y, Suzuki S, Matsuda K, Toda K, Isshiki N. A new skin equivalent: keratinocytes proliferated and differentiated on collagen sponge containing fibroblasts. Plast Reconstr Surg 1994;93:537-546; Medalie DA, Eming SA, Collins ME, Tompkins RG, Yarmush ML, Morgan JR. Differences in dermal analogs influence subsequent pigmentation, epidermal differentiation, basement membrane, and rete ridge formation of transplanted composite skin grafts. Transplantation 1997;64:454-465).

Thus, the Lee paper supports this previous work, but other work suggests that DFs may not help patients with diabetes mellitis and have chronic wounds (Wu Y, Chen L, Scott PG, Tredget EE. Mesenchymal stem cells enhance wound healing through differentiation and angiogenesis. Stem Cells 2007;25:2648-2659).  Therefore, even though DFs seem to accelerate wound healing in non-diabetic mice, ADSCs are able to accelerate wound healing in diabetic mice, and therefore might be even more useful for patients.

Furthermore, DFs have other clinical limitations in that they must be isolated from a patient’s own skin.  Also, the ability of DFs to be detected by the immune system could also limit their ability to heal wounds.  ADSCs, on the other hand, are easily isolated by liposuction, are poorly recognized by the immune system, and might accelerate wound healing.  In conclusion, ADSCs might provide a treatment regime for chronic wounds and help those who suffer from such things experience wound closure.