New MSC: MSCs as pericytes are Sentinels and gatekeepers

Abstract

Human Mesenchymal Stem Cells, hMSCs, were first named over 25 years ago with the "stem cell" nomenclature derived from the fact that we and others could cause these cells to differentiate into a number of different mesodermal phenotypes in cell culture. The capacity to form skeletal tissue in vitro encouraged the use of hMSCs for the fabrication of tissue engineered skeletal repair tissue with subsequent transplantation to in vivo sites. With the current realization that MSCs are derived from perivascular cells, pericytes, and the immunomodulatory and trophic capabilities of MSCs in both in vitro and in vivo test systems, a complete re-evaluation of the role and functions of MSCs in the body was required. Additionally, the skeleton is a preferred organ for cancer dissemination from various tumor malignancies. To date, most efforts to understand skeletal metastasis have focused on the invasive and digestive capability of disseminated tumor cells (DTCs). The contribution of the target organ-specific microvascular structure influencing extravasation is less well understood. Current targeted cancer therapies are designed to alter not only biological functions in DTCs, but also components of the tumor stroma/microenvironment such as blood vessels. We now have a comprehensive image of the critical role of the host vasculature as an instructive niche for DTCs. The focus of this manuscript is to present the current information about MSC function in situ and to emphasize how these new observations provide insight into understanding the role of the pericyte/MSC in skeletal activities including our new hypothesis for how these cells act as a gatekeeper for metastasis of melanoma into bone. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1151-1159, 2017.

Rescue from lethal acute radiation syndrome (ARS) with severe weight loss by secretome of intramuscularly injected human placental stromal cells

“…By FACS analysis, these cells were negative to haematopoietic end endothelial markers, expressing surface marker profile identical to mesenchymal stromal cells from other sources. Those include also CD146 and CD166 which are shared with other cell types including pericytes, which are proposed to be the source of mesenchymal stromal cells ( Figure ). The PLX‐RAD cells in all the treated groups were injected on days 1 and 4 after the mice irradiation.…”

“…The cells are positive to CD146 and 166 which are also shared with other cell types like pericytes. source of mesenchymal stromal cells [63][64][65] (Figure 2). The PLX-RAD cells in all the treated groups were injected on days 1 and 4 after the mice irradiation.…”

JOR Virtual Issue on stem cells in orthopaedics

“…A second question is: What are stem cells actually doing? Our contemporary idea of what stem cells can do has evolved from tissue repair by the stem cells themselves differentiating in vivo into a specific tissue, to the use of stem cells to provide the necessary environment for repair, such as reducing inflammation at the repair site or providing “growth factors” for repair . A third question is: How will stem cells be used clinically?…”

“…While originally considered to be of bone marrow origin, it is now thought that mesenchymal stem cells (MSCs) are actually derived from perivascular cells called pericytes. 3 While populations of these cells exist in many tissues, muscle stem cells, 4 synovial stem cells, 5-7 bone marrow [8][9][10][11] ; nucleus pulposus, 12,13 umbilical cord, 14 adipose and tendon. 15,16 A second question is: What are stem cells actually doing?…”

“…Our contemporary idea of what stem cells can do has evolved from tissue repair by the stem cells themselves differentiating in vivo into a specific tissue, to the use of stem cells to provide the necessary environment for repair, such as reducing inflammation at the repair site or providing "growth factors" for repair. 3 A third question is: How will stem cells be used clinically? Stem cells can be used alone, 5 used with scaffold material 10,13,14 or induction factors 17 or in combination with other methods such as joint distraction.…”