Potential therapeutic applications of mesenchymal stromal cells (original) (raw)

Mesenchymal stem cells: immunobiology and role in immunomodulation and tissue regeneration

Cytotherapy, 2009

Mesenchymal stem cells (MSC) are multipotent cells that differentiate into osteoblasts, myocytes, chondrocytes and adipocytes as well as insulin-producing cells. The mechanism underlying their in vivo differentiation is not clear and is thought to be caused by spontaneous cell fusion or factors present in the microenvironment. However, their ease of isolation, high 'ex-vivo' expansion potential and ability to differentiate into multiple lineages make them attractive tools for potential use in cell therapy. MSC have been isolated from several tissues, including bone/bone marrow, fat, Wharton's jelly, umbilical cord blood, placenta and pancreas. The 'immunosuppressive' property of human MSC makes them an important candidate for cellular therapy in allogeneic settings. Use of allogeneic MSC for repair of large defects may be an alternative to autologous and allogeneic tissue-grafting procedures. An allogeneic approach would enable MSC to be isolated from any donor, expanded and cryopreserved, providing a readily available source of progenitors for cell replacement therapy.

Mesenchymal stromal cells for organ transplantation

Current Opinion in Organ Transplantation, 2014

Purpose of the review In this review, recent findings on the effects of tissue and donor origin, culturing conditions and preconditioning regimens on the therapeutic effect of mesenchymal stem cells (MSC) in organ transplantation are discussed and the importance of understanding the characteristics of MSC for developing efficient therapy is stressed.

Immunomodulatory nature and site specific affinity of mesenchymal stem cells: A hope in cell therapy

2014

markers such as CD34, CD45, CD11 or CD14 or costimulatory molecules, CD40, CD80, and CD86 while express CD166, CD29, CD106, and ICAM-1 in various status. 11-17 The International Society for Cellular Therapy (ISCT) has offered several criteria to identify MSCs which are listed as: 1) Plastic adherence while maintaining these cells in standard conditions. 2) Expression of CD73, CD90 and CD105 markers in at least 95% of cell population and lack expression of CD34, CD45, CD14 orCD11b, CD19 or CD79α and HLA-II markers as measured by flow cytometry. 3) Differentiation capability in to adipogenic, osteogenic and chondrogenic lineage cells in vitro. 18,19 Recent publication is considered exceptions for identifying adipose tissue-derived stromal cells (ASC) and adipose tissue's stromal vascular fraction (SVF) cells. 20 It has been revealed that ASC, similar to the other MSCs, have tri-lineage differentiation potency with a set of markers phenotype (CD73 + , CD90 + , CD105 + , CD36 + , CD44 + , CD106-, CD45-, and CD31-) to distinguish them from bone marrow MSCs. In order to identify the SVFs, these cells are characterizes by the (CD34+, CD45-, CD31-, CD235a-) phenotype and fibroblastoid colony-forming unit assay. 20 In addition to the bone marrow, 21,22 MSCs have been found in other sources, including liver, 23 lung, 24,25 brain, 26 adipose tissue, 22,27-29 peripheral blood, 30 cornea, 31 synovium, 32 thymus, 33 dental pulp, 34,35 periosteum, 36 tendon, 37 spleen, 33 fallopian tube, 38 placenta, 39,40 amniotic fluid, 41 Wharton's jelly, 42 umbilical cord 43,44 and umbilical cord blood. 22,45

Mesenchymal Stromal Cells in Solid Organ Transplantation

Transplantation, 2019

MSCs represent a heterogeneous population of fibroblast-like cells whose definition relies on the combination of the following criteria, according to the International Society for Cellular Therapy 4 : (1) adherence to plastic, (2) specific surface antigen expression of CD105, CD73, and CD90 and lack of expression of CD45, CD34, CD14 and/ Abstract. Over the past decade, the clinical application of mesenchymal stromal cells (MSCs) has generated growing enthusiasm as an innovative cell-based approach in solid organ transplantation (SOT). These expectations arise from a significant number of both transplant-and non-transplant-related experimental studies investigating the complex antiinflammatory, immunomodulatory, and tissue-repair properties of MSCs. Promising preclinical results have prompted clinical trials using MSC-based therapy in SOT. In the present review, the general properties of MSCs are summarized, with a particular emphasis on MSC-mediated impact on the immune system and in the ischemic conditioning strategy. Next, we chronologically detail all clinical trials using MSCs in the field of SOT. Finally, we envision the challenges and perspectives of MSC-based cell therapy in SOT.

Potential of mesenchymal stem cells as immune therapy in solid-organ transplantation

Transplant International, 2009

What is already known? Characteristics of MSCs Over the last decade, various medical disciplines have become increasingly interested in mesenchymal stem cells (MSCs), whose unique characteristics are potentially useful for clinical therapy. MSCs are present in most tissues, including bone marrow, adipose tissue, skin, placenta and heart [1-5], and can be isolated and expanded ex vivo. They are selected on the basis of their capacity to adhere to plastic, and are characterized by their fibroblast-like morphology in culture, immunophenotype and multilineage differentiation capacity [1,2]. As no specific marker for MSCs has been found yet, MSCs are identified by a panel of cell-surface markers, including CD29, CD44, CD73 (SH3/4), CD90 (Thy-1), CD105 (SH2), CD106 (VCAM-1), CD166 (ALCAM) and HLA class-I. MSCs do not express hematopoietic or endothelial lineage markers such as CD11b, CD14, CD31, CD34, or CD45 [1,6,7]. Also, unless they are stimulated with IFN-c, MSCs do not express the co-stimulatory molecules CD80 and CD86 or HLA class-II [8,9]. One of the main functional properties of MSCs is their capacity to differentiate into a variety of specialized cell types, such as osteoblasts, chondrocytes, adipocytes, myocytes (Fig. 1) or neuronal precursors cells [1,10,11]. This capacity makes them promising candidates for use in regenerative medicine. Human and animal studies have shown that MSCs have potential to repair bone [12,13], cartilage [14,15], skin [16,17], and neuronal tissue [18] and improve the function of cardiac muscle [19-21] and the kidney [22]. Recent clinical trials are investigating the use of MSCs in treating heart disease, liver cirrhosis and bone fractures. It is unclear whether MSCs contribute to tissue repair by differentiation into tissue-specific cell types, or whether they produce trophic factors at the site of injury, which either stimulate tissue-repair [23,24] or which conceivably reduce self-inflicting damage by the immune system. In addition to their capacity for multilineage

Mesenchymal Stem/Stromal Cells in Organ Transplantation

Pharmaceutics

Organ transplantation is essential and crucial for saving and enhancing the lives of individuals suffering from end-stage organ failure. Major challenges in the medical field include the shortage of organ donors, high rates of organ rejection, and long wait times. To address the current limitations and shortcomings, cellular therapy approaches have been developed using mesenchymal stem/stromal cells (MSC). MSC have been isolated from various sources, have the ability to differentiate to important cell lineages, have anti-inflammatory and immunomodulatory properties, allow immunosuppressive drug minimization, and induce immune tolerance towards the transplanted organ. Additionally, rapid advances in the fields of tissue engineering and regenerative medicine have emerged that focus on either generating new organs and organ sources or maximizing the availability of existing organs. This review gives an overview of the various properties of MSC that have enabled its use as a cellular th...

REVIEW Mesenchymal stem cells: immunobiology and role in immunomodulation and tissue regeneration

2014

Mesenchymal stem cells (MSC) are multipotent cells that differentiate into osteoblasts, myocytes, chondrocytes and adipocytes as well as insulin-producing cells. The mechanism underlying their in vivo differentiation is not clear and is thought to be caused by spontaneous cell fusion or factors present in the microenvironment. However, their ease of isolation, high ‘ex-vivo ’ expansion potential and ability to differentiate into multiple lineages make them attractive tools for potential use in cell therapy. MSC have been isolated from several tissues, including bone/bone marrow, fat, Wharton’s jelly, umbilical cord blood, placenta and pancreas. The ‘immunosuppressive’ property of human MSC makes them an important candidate for cellular therapy in allogeneic settings. Use of allogeneic MSC for repair of large defects may be an alternative to autologous and allogeneic tissue-grafting procedures. An allogeneic approach would enable MSC to be isolated from any donor, expanded and cryopr...