Biomedical subjects

Frank P Barry

Publications and source records attributed to Frank P Barry.

6 recordsLinked to original sources

PubMed2005

Mesenchymal stem cells avoid allogeneic rejection.

Adult bone marrow derived mesenchymal stem cells offer the potential to open a new frontier in medicine. Regenerative medicine aims to replace effete cells in a broad range of conditions associated with damaged cartilage, bone, muscle, tendon and ligament. However the normal process of immune rejection of mismatched allogeneic tissue would appear to prevent the realisation of such ambitions. In fact mesenchymal stem cells avoid allogeneic rejection in humans and in animal models. These finding are supported by in vitro co-culture studies. Three broad mechanisms contribute to this effect. Firstly, mesenchymal stem cells are hypoimmunogenic, often lacking MHC-II and costimulatory molecule expression. Secondly, these stem cells prevent T cell responses indirectly through modulation of dendritic cells and directly by disrupting NK as well as CD8+ and CD4+ T cell function. Thirdly, mesenchymal stem cells induce a suppressive local microenvironment through the production of prostaglandins and interleukin-10 as well as by the expression of indoleamine 2,3,-dioxygenase, which depletes the local milieu of tryptophan. Comparison is made to maternal tolerance of the fetal allograft, and contrasted with the immune evasion mechanisms of tumor cells. Mesenchymal stem cells are a highly regulated self-renewing population of cells with potent mechanisms to avoid allogeneic rejection.

Journal Article↗

PubMed2005

Immunogenicity of adult mesenchymal stem cells: lessons from the fetal allograft.

Herein we review recent data that support host tolerance of allogeneic adult mesenchymal stem cells (MSC). Evidence is emerging that donor MSC deploy a very powerful array of mechanisms that allow escape from host allogeneic responses. These mechanisms include limited expression of alloantigen by the stem cell and cell contact-dependent and -independent mechanisms. MSC modulate host dendritic cell and T cell function, promoting induction of suppressor or regulatory T cells. These effects are complemented by the induction of divisional arrest anergy in T cells and by stem cell production of soluble immunomodulatory factors, including interleukin-10, transforming growth factor-beta, prostaglandin E2, and hepatocyte growth factor. In addition, MSC express the enzyme indoleamine 2,3-dioxygenase, which creates a tryptophan-depleted milieu that promotes immunosuppression. We propose that these observations show striking similarity to emerging data on the maternal acceptance of the fetal allograft. This comparison suggests new approaches to determine the contribution of different mechanisms to the successful use of MSC in regenerative medicine.

Adult↗

PubMed2004

Mesenchymal stem cells: clinical applications and biological characterization.

Mesenchymal stem cells (MSCs) have been isolated from bone marrow, periosteum, trabecular bone, adipose tissue, synovium, skeletal muscle and deciduous teeth. These cells have the capacity to differentiate into cells of connective tissue lineages, including bone, fat, cartilage and muscle. A great deal has been learned in recent years about the isolation and characterization of MSCs, and control of their differentiation. These cells have generated a great deal of interest because of their potential use in regenerative medicine and tissue engineering and there are some dramatic examples, derived from both pre-clinical and clinical studies, that illustrate their therapeutic value. This review summarizes recent findings regarding the potential clinical use of MSCs in cardiovascular, neural and orthopaedic applications. As new methods are developed, there are several aspects to the implanted cell-host interaction that need to be addressed before we can fully understand the underlying mechanisms. These include the host immune response to implanted cells, the homing mechanisms that guide delivered cells to a site of injury and the differentiation in vivo of implanted cells under the influence of local signals.

Animals↗

PubMed2003

Stem cell therapy in a caprine model of osteoarthritis.

OBJECTIVE: To explore the role that implanted mesenchymal stem cells may play in tissue repair or regeneration of the injured joint, by delivery of an autologous preparation of stem cells to caprine knee joints following induction of osteoarthritis (OA). METHODS: Adult stem cells were isolated from caprine bone marrow, expanded in culture, and transduced to express green fluorescent protein. OA was induced unilaterally in the knee joint of donor animals by complete excision of the medial meniscus and resection of the anterior cruciate ligament. After 6 weeks, a single dose of 10 million autologous cells suspended in a dilute solution of sodium hyaluronan was delivered to the injured knee by direct intraarticular injection. Control animals received sodium hyaluronan alone. RESULTS: In cell-treated joints, there was evidence of marked regeneration of the medial meniscus, and implanted cells were detected in the newly formed tissue. Degeneration of the articular cartilage, osteophytic remodeling, and subchondral sclerosis were reduced in cell-treated joints compared with joints treated with vehicle alone without cells. There was no evidence of repair of the ligament in any of the joints. CONCLUSION: Local delivery of adult mesenchymal stem cells to injured joints stimulates regeneration of meniscal tissue and retards the progressive destruction normally seen in this model of OA.

Animals↗

PubMed2003

Biology and clinical applications of mesenchymal stem cells.

Stem cell populations are found in most adult tissues and, in general, their differentiation potential may reflect the local cell population. Hematopoietic, epidermal, mesenchymal, neural and hepatic stem cells have been described. It may be that, in the adult, these cells are the reservoirs of reparative cells that are mobilized following injury and migrate to the wound site where, in cooperation with local cells, they participate in the repair response. Mesenchymal stem cells, isolated from the bone marrow, have the capacity to differentiate into cells of connective tissues. Some striking examples of the therapeutic use of MSCs have been reported recently in applications such as coronary artery disease, spinal cord injury, Parkinson's Disease, and liver regeneration. In orthopaedic medicine, MSC therapy has been applied in bone and cartilage repair and in the treatment of osteoarthritis. The question of the host response to implanted MSCs is critical as these cells are being evaluated in clinical applications. There are several aspects to the implanted cell-host interaction that need to be addressed as we attempt to understand the mechanisms underlying stem cell therapies. These are (1) the host immune response to implanted cells, (2) the homing mechanisms that guide delivered cells to a site of injury, and (3) differentiation of implanted cells under the influence of local signals.

Animals↗

PubMed2003

Mesenchymal stem cell therapy in joint disease.

Mesenchymal stem cells have the capacity to differentiate into a variety of connective tissue cells including bone, cartilage, tendon, muscle and adipose tissue. These multipotent cells have been isolated from bone marrow and from other adult tissues including skeletal muscle, fat and synovium. Because of their multipotentiality and capacity for self renewal adult stem cells may represent units of active regeneration of tissues damaged as a result of trauma or disease. In certain degenerative diseases such as osteoarthritis (OA) stem cells are depleted, and have reduced proliferative capacity and reduced ability to differentiate. The delivery of stem cells to these individuals may therefore enhance repair or inhibit the progressive destruction of the joint. We have developed methods for the delivery of mesenchymal stem cell preparations taken from bone marrow to the injured knee joint. This treatment has the potential to stimulate regeneration of cartilage and retard the progressive destruction of the joint that typically occurs following injury.

Adult↗