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Mesenchymal Stem Cells



Signalling behind MSC Mobilisation Uncovered

Original article from STEM CELLS

“Injury-Activated Transforming Growth Factor β Controls Mobilization of Mesenchymal Stem Cells for Tissue Remodeling”

Adult stem/progenitor cells are able to differentiate into many cell types and can also be recruited to a site of injury where they either repair the injured tissue or contribute to tissue remodeling (Ferrari et al, Takahashi et al,Lagasse et al, Orlic et al and Kale et al). Mesenchymal stem cells (MSCs) in peripheral blood are one such stem cell known to act in this way, and it is believed that promigratory factors released from injured tissue or surrounding inflammatory cells create a signal for their recruitment (Caplan and Correa, Krankel et al and Wojakowski et al). However the primary endogenous factors activated or released in response to injury to stimulate the mobilization of MSCs are largely unknown. Transforming growth factor beta proteins (TGFβs) are synthesized in a latent form sequestered in extracellular matrix (ECM) (Kanzaki et al and Munger et al) and perturbations in the ECM associated with phenomena such as angiogenesis, wound repair, inflammation, and cell growth (Annes et al) release active TGFβs. TGFβ1 can be released from the bone matrix to induce MSCs migration for bone remodeling (Tang et al), but less is understood about a potential role in the vasculature where shear stress and arterial injury can induce activation of TGFβ1 (Ahamed et al and Qi et al). Now, in a study in Stem Cells, researchers from the group of Xu Cao at the Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA, using two separate models of arterial damage, have found that MSCs become mobilized into peripheral blood and migrate to injured sites to participate in vascular repair and remodeling by a mechanism controlled by active TGFβ1 (Wan et al).

Stem Cell Transplant Down to a T - Mesenchymal stem cell–based tissue regeneration is governed by recipient T lymphocytes via IFNγ and TNFα

From Nature Medicine
By Stuart P. Atkinson

Bone marrow mesenchymal stem cells (BMMSCs) are multipotent adult stem cells which are capable of differentiating into various cell types (osteoblasts, adipocytes and chondrocytes (Friedenstein et al, Pittinger et al and Prockop)) and their regenerative capabilities shown to be of clinical importance in the treatment of bone and bone-associated tissue disease (Caplan, García-Gómez et al, Tasso et al and Bueno and Glowacki). Further, BMMSCs have been shown to interact with immune cells to aid bone regeneration but the specific function of recipient immune cells has not been assessed. Now, researchers from the laboratory of Songtao Shi at the University of Southern California, USA, have found that recipient immune cells, specifically T cells, govern BMMSC-based tissue regeneration using an established in vivo BMMSC implantation system (Liu et al).

Dedifferentiation-Reprogrammed Mesenchymal Stem Cells with Improved therapeutic Potential

Original article from STEM CELLS

Recent studies have demonstrated that mesenchymal stem cells (MSCs) have the ability to differentiate into various kinds of cell types, including neuron-like cells in culture (Woodbury et al, Qian and Saltzman, Levy et al and Rismanchi et al) which has been further verified by transplantation experiments in various animal models of human disease. However, these studies have been hampered by reported low levels of cell persistence, neuronal differentiation in vivo and massive death of transplanted cells limiting their overall effectiveness and clinical use. Dedifferentiation is a process by which differentiated cells are reverted to an earlier, more primitive phenotype which confers an extended differentiation potential (Odelberg, Kollhoff and Keating) and previous studies by the authors of the study discussed herein demonstrated that by withdrawal of extrinsic stimulation, MSC-derived neurons are able to revert back to MSC morphologically (Woodbury, Reynold and Black and Li et al), but whether these dedifferentiated MSCs (DeMSCs) were similar to MSCs was unknown. This point is now addressed in the December issue of Stem Cells in a study (Liu et al) from the laboratories of Hsiao Chang Chan (Chinese University of Hong Kong, Shatin, Hong Kong) and Tingyu Li (Chongqing Medical University, Chongqing, China).

Debrided Skin as a Source of Autologous Stem Cells for Wound Repair

From the August Edition of Stem Cells
Paper commentary by Stuart P. Atkinson

Tissue resident adult stem cells, such as mesenchymal stem cells (MSCs) or adipose-derived stem cells (ASCs), have previously demonstrated a capacity to repair extensively injured tissues (Picinich et al, Horwitz and Dominici). However, major traumatic injuries such as large surface area burns, which constitute 5%–10% of military casualties, limit the availability of autologous stem cell populations for wound repair and such injuries also require extensive reconstruction. The process of wound debridement; the medical removal of a patient's dead, damaged, or infected tissue to improve the healing potential of the remaining healthy tissue, typically involves the removal of subcutaneous layers and associated tissue structures, including portions of intact hypodermal adipose tissue. This led the group of Robert J. Christy at the United States Army Institute of Surgical Research, Fort Sam Houston, Texas, USA to investigate the potential of debrided skin to be a source of viable autologous stem cells for use in wound treatments. Their report (Natesan et al) is published in the August Edition of Stem Cells.


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