musculoskeletal disorders, among others. other areas of orthopedic research for uses of mscs include tissue engineering and regenerative medicine. wound healing stem cells can also be used to stimulate the growth of human tissues. in an adult, wounded tissue is most often replaced by scar tissue, which is characterized in the skin by disorganized collagen structure, loss of hair follicles and irregular vascular structure. in the case of wounded fetal tissue, however, wounded tissue is replaced with normal tissue through the activity of stem cells. a possible method for tissue regeneration in adults is to place adult stem cell "seeds" inside a tissue bed "soil" in a wound bed and allow the stem cells to stimulate differentiation in the tissue bed cells. this method elicits a regenerative response more similar to fetal wound-healing than adult scar tissue formation. researchers are still investigating different aspects of the "soil" tissue that are conducive to regeneration. because of the general healing capabilities of stem cells, they have gained interest for the treatment of cutaneous wounds, such as in skin cancer. hiv/aids destruction of the immune system by the hiv is driven by the loss of cd4+ t cells in the peripheral blood and lymphoid tissues. viral entry into cd4+ cells is mediated by the interaction with a cellular chemokine receptor, the most common of which are ccr5 and cxcr4. because subsequent viral replication requires cellular gene expression processes, activated cd4+ cells are the primary targets of productive hiv infection. recently scientists have been investigating an alternative approach to treating hiv-1/aids, based on the creation of a disease-resistant immune system through transplantation of autologous, gene-modified (hiv-1-resistant) hematopoietic stem and progenitor cells (gm-hspc). regenerative treatment models stem cells are thought to mediate repair via five primary mechanisms: 1) providing an anti-inflammatory effect, 2) homing to damaged tissues and recruiting other cells, such as endothelial progenitor cells, that are necessary for tissue growth, 3) supporting tissue remodeling over scar formation, 4) inhibiting apoptosis, and 5) differentiating into bone, cartilage, tendon, and ligament tissue. to further enrich blood supply to the damaged areas, and consequently promote tissue regeneration, platelet-rich plasma could be used in conjunction with stem cell transplantation. the efficacy of some stem cell populations may also be affected by the method of delivery; for instance, to regenerate bone, stem cells are often introduced in a scaffold where they produce the minerals necessary for generation of functional bone. stem cells have also been shown to have a low immunogenicity due to the relatively low number of mhc molecules found on their surface. in addition, they have been found to secrete chemokines that alter the immune response and promote tolerance of the new tissue. this allows for allogeneic treatments to be performed without a high rejection risk. drug discovery and biomedical research the ability to grow up functional adult tissues indefinitely in culture through directed differentiation creates new opportunities for drug research. researchers are able to grow up differentiated cell lines and then test new drugs on each cell type to examine possible interactions in vitro before performing in vivo studies. this is critical in the development of drugs for use in veterinary research because of the possibilities of species-specific interactions. the hope is that having these cell lines available for research use will reduce the need for research animals used because effects on human tissue in vitro will provide insight not normally known before the animal testing phase. with the advent of induced pluripotent stem cells (ipsc), treatments being explored and created for the used in endangered low production animals possible. rather than needing to harvest embryos or eggs, which are limited, the researchers can remove mesenchymal stem cells with greater ease and greatly reducing the danger to the animal due to noninvasive techniques. this allows the limited eggs to be put to use for reproductive purposes only. conservation stem cells are being explored for use in conservation efforts. spermatogonial stem cells have been harvested from a rat and placed into a mouse host and fully mature sperm were produced with the ability to produce viable offspring. currently research is underway to find suitable hosts for the introduction of donor spermatogonial stem cells. if this becomes a viable option for conservationists, sperm can be produced from high genetic quality individuals who die before reaching sexual maturity, preserving a line that would otherwise be lost. sources for stem cells most stem cells intended for regenerative therapy are generally isolated either from the patient's bone marrow or from adipose tissue. mesenchymal stem cells can differentiate into the cells that make up bone, cartilage, tendons, and ligaments, as well as muscle, neural and other progenitor tissues. they have been the main type of stem cells studied in the treatment of diseases affecting these tissues. the number of stem cells transplanted into damaged tissue may alter the efficacy of treatment. accordingly, stem cells derived from bone marrow aspirates, for instance, are cultured in specialized laboratories for expansion to millions of cells. although adipose-derived tissue also requires processing prior to use, the culturing methodology for adipose-derived stem cells is not as extensive as that for bone marrow-derived cells. while it is thought that bone-marrow-derived stem cells are preferred for bone, cartilage, ligament, and tendon repair, others believe that the less challenging collection techniques and the multi-cellular microenvironment already present in adipose-derived stem cell fractions make the latter the preferred source for autologous transplantation. new sources of mesenchymal stem cells are being researched, including stem cells present in the skin and dermis which are of interest because of the ease at which they can be harvested with minimal risk to the animal. hematopoietic stem cells have also been discovered to be travelling in the blood stream and possess equal differentiating ability as other mesenchymal stem cells, again with a very non-invasive harvesting technique. there has been more recent interest in the use of extra embryonic mesenchymal stem cells. research is underway to examine the differentiating capabilities of stem cells found in the umbilical cord, yolk sac and placenta of different animals. these stem cells are thought to have more differentiating ability than their adult counterparts, including the ability to more readily form tissues of endodermal and ectodermal origin. embryonic stem cell lines there is widespread controversy over the use of human embryonic stem cells. this controversy primarily targets the techniques used to derive new embryonic stem cell lines, which often requires the destruction of the blastocyst. opposition to the use of human embryonic stem cells in research is often based on philosophical, moral, or religious objections. there is other stem cell research that does not involve the destruction of a human embryo, and such research involves adult stem cells, amniotic stem cells, and induced pluripotent stem cells. on 23 january 2009, the us food and drug administration gave clearance to geron corporation for the initiation of the first clinical trial of an embryonic stem-cell-based therapy on humans. the trial aimed to evaluate the drug grnopc1, embryonic stem cell-derived oligodendrocyte progenitor cells, on people with acute spinal cord injury. the trial was discontinued in november 2011 so that the company could focus on therapies in the "current environment of capital scarcity and uncertain economic conditions". in 2013 biotechnology and regenerative medicine company biotime (amex: btx) acquired geron's stem cell assets in a stock transaction, with the aim of restarting the clinical trial. mesenchymal stromal cells (mscs) scientists have reported that mscs when transfused immediately within few hours post thawing may show reduced function or show decreased efficacy in treating diseases as compared to those mscs which are in log phase of cell growth (fresh), so cryopreserved mscs should be brought back into log phase of cell growth in invitro culture before administration. re-culturing of mscs will help in recovering from the shock the cells get during freezing and thawing. various msc clinical trials which used cryopreserved product immediately post thaw have failed as compared to those clinical trials which used fresh mscs. veterinary medicine research has been conducted on horses, dogs, and cats can benefit the development of stem cell treatments in veterinary medicine and can target a wide range of injuries and diseases such as myocardial infarction, stroke, tendon and ligament damage, osteoarthritis, osteochondrosis and muscular dystrophy both in large animals, as well as humans. while investigation of cell-based therapeutics generally reflects human medical needs, the high degree of frequency and severity of certain injuries in racehorses has put veterinary medicine at the forefront of this novel regenerative approach. companion animals can serve as clinically relevant models that closely mimic human disease. sources of stem cells veterinary applications of stem cell therapy as a means of tissue regeneration have been largely shaped by research that began with the use of adult-derived mesenchymal stem cells to treat animals with injuries or defects affecting bone, cartilage, ligaments and/or tendons. there are two main categories of stem cells used for treatments: allogeneic stem cells derived from a genetically different donor within the same species and autologous mesenchymal stem cells, derived from the patient prior to use in various treatments. a third category, xenogenic stem cells, or stem cells derived from different species, are used primarily for research purposes, especially for human treatments. bone repair bone has a unique and well documented natural healing process that normally is sufficient to repair fractures and other common injuries. misaligned breaks due to severe trauma, as well as treatments like tumor resections of bone cancer, are prone to improper healing if left to the natural process alone. scaffolds composed of natural and artificial components are seeded with mesenchymal stem cells and placed in the defect. within four weeks of placing the scaffold, newly formed bone begins to integrate with the old bone and within 32 weeks, full union is achieved. further studies are necessary to fully characterize the use of cell-based therapeutics for treatment of bone fractures. stem cells have been used to treat degenerative bone diseases. the normally recommended treatment for dogs that have legg–calve–perthes disease is to remove the head of the femur after the degeneration has progressed. recently, mesenchymal stem cells have been injected directly in to the head of the femur, with success not only in bone regeneration, but also in pain reduction. ligament and tendon repair autologous stem cell-based treatments for ligament injury, tendon injury, osteoarthritis, osteochondrosis, and sub-chondral bone cysts have been commercially available to practicing veterinarians to treat horses since 2003 in the united states and since 2006 in the united kingdom. autologous stem cell based treatments for tendon injury, ligament injury, and osteoarthritis in dogs have been available to veterinarians in the united states since 2005. over 3000 privately owned horses and dogs have been treated with autologous adipose-derived stem cells. the efficacy of these treatments has been shown in double-blind clinical trials for dogs with osteoarthritis of the hip and elbow and horses with tendon damage. race horses are especially prone to injuries of the tendon and ligaments. conventional therapies are very unsuccessful in returning the horse to full functioning potential. natural healing, guided by the conventional treatments, leads to the formation of fibrous scar tissue that reduces flexibility and full joint movement. traditional treatments prevented a large number of horses from returning to full activity and also have a high incidence of re-injury due to the stiff nature of the scarred tendon. introduction of both bone marrow and adipose derived stem cells, along with natural mechanical stimulus promoted the regeneration of tendon tissue. the natural movement promoted the alignment of the new fibers and tendocytes with the natural alignment found in uninjured tendons. stem cell treatment not only allowed more horses to return to full duty and also greatly reduced the re-injury rate over a three-year period. the use of embryonic stem cells has also been applied to tendon repair. the embryonic stem cells were shown to have a better survival rate in the tendon as well as better migrating capabilities to reach all areas of damaged tendon. the overall repair quality was also higher, with better tendon architecture and collagen formed. there was also no tumor formation seen during the three-month experimental period. long-term studies need to be carried out to examine the long-term efficacy and risks associated with the use of embryonic stem cells. similar