Mesenchymal stem cell and regenerative medicine: regeneration versus immunomodulatory challenges - PubMed (original) (raw)

Mesenchymal stem cell and regenerative medicine: regeneration versus immunomodulatory challenges

Sujata Law et al. Am J Stem Cells. 2013.

Abstract

Mesenchymal Stem cells (MSC) are now presented with the opportunities of multifunctional therapeutic approaches. Several reports are in support of their self-renewal, capacity for multipotent differentiation, and immunomodulatory properties. They are unique to contribute to the regeneration of mesenchymal tissues such as bone, cartilage, muscle, ligament, tendon, and adipose. In addition to promising trials in regenerative medicine, such as in the treatment of major bone defects and myocardial infarction, MSC has shown a therapeutic effect other than direct hematopoiesis support in hematopoietic reconstruction. MSCs are identified by the expression of many molecules including CD105 (SH2) and CD73(SH3/4) and are negative for the hematopoietic markers CD34, CD45, and CD14. Manufacturing of MSC for clinical trials is also an important aspect as their differentiation, homing and Immunomodulatory properties may differ. Their suppressive effects on immune cells, including T cells, B cells, NK cells and DC cells, suggest MSCs as a novel therapy for GVHD and other autoimmune disorders. Since the cells by themselves are non-immunogenic, tissue matching between MSC donor and recipient is not essential and, MSC may be the first cell type able to be used as an "off-the-shelf" therapeutic product. Following a successful transplantation, the migration of MSC to the site of injury refers to the involvement of chemokines and chemokine receptors of respective specificity. It has been demonstrated that cultured MSCs have the ability to engraft into healthy as well as injured tissue and can differentiate into several cell types in vivo, which facilitates MSC to be an ideal tool for regenerative therapy in different disease types. However, some observations have raised questions about the limitations for proper use of MSC considering some critical factors that warn regular clinical use.

Keywords: MSC application limitations; MSC therapy; Mesenchymal stem cell; immunology.

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Figures

Figure 1

Figure 1

Enumeration of Bone Marrow derived adherent stromal cells/MSC with transforming characters: A. Whole bone marrow cells when cultured for more than 3 days in RPMI-1640 + 30% Fetal Bovine Serum (FBS) generated large stromal precursor cells with decaying HSCs and others. These precursor cells were tentatively transformed to stromal fibroblasts while HSCs were totally exhausted. B. The culture on subsequent days (after 9 days) represented significant transformation of the precursors into spindle shaped stromal fibroblasts with changes in morphology. The Generation of stromal fibroblasts from the precursors were in steady state. These cells were supposed to represent the bone marrow derived MSC. C. Elongated fibroblastic stromal appearance was apparent after 15 days of culture. The plate showed full confluence and considered to be matured stromal fibroblasts or Mesenchymal Stem cells (MSC).

Figure 2

Figure 2

Schematics for MSC (Mesenchymal Stem Cell) therapy and the challenges: Therapeutic benefits of MSCs are varied but awaits full clinical success. The obstacles are required to be removed with proper monitoring and educating the cells with verified protocols.

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