More to Explore; The Mesenchymal Stem Cells (MSCs) Major Tissue Sources, Known Surface Markers and Its Immunomodulation properties

Mesenchymal stem cells (MSCs) are currently available for a range of applications and have become a good material for regenerative medicine, tissue engineering, and disease therapy. MSCs are self-renewing, multipotent progenitor cells with multilineage potential to differentiate into cell types of mesodermal origin, such as adipocytes, osteocytes, and chondrocytes and exert potent immunosuppressive potentials. In the present review, we highlight the currently reported variations in the differentiation potential of MSCs from different tissue sources, the minimal criteria to define MSCs from various tissue environments and provide a detailed description of MSCs surface markers. Furthermore, MSCs immunomodulatory features secrete cytokines and immune receptors which regulate the microenvironment in the host tissue also revisits in detail. We propose that there are likely more sources of MSCs waiting to be discovered. We need to Standardize MSCs characterization by selecting markers for isolation, cellular and molecular mechanisms involved in MSCmediated immune modulation, and other functionalities of MSCs should be characterized prior to use in clinical

fication of human MSC (hMSC). In 2006 a set of markers and cell characteristics has been proposed by the International Society for Cellular Therapy has proposed minimum criteria to define MSCs as these cells (a) should exhibits plastic adherence; (b) possess specific set of cell surface markers, i.e. cluster of differentiation CD73, D90, CD105 and lack expression of CD14, CD34, CD45 and human leucocyte antigen-DR (HLA-DR); and (c) have the ability to differentiate in-vitro into adipocyte, chondrocyte and osteoblast (Crisan et al., 2008). The availability and culturally expandable in vitro with special genomic stability and less ethical issues, marking these incredible cells importance in cell regenerative therapy and medicine (Dominici et al., 2006;Ullah et al., 2015). The resent study is the concise review article to gather available the information about stem cell sources, identification makers, Paracrine secretion, Immunomodulation by MSCs and their importance in regenerative therapies.

Human Mesenchymal Stem Cell (HMSC) Sources:
The bone marrow (BM) has been the prevailing source of MSCs in humans (Mushahary et al., 2018). However, while BM is a rich source of hematopoietic stem cells, it constitutes only a rare MSC population (Li et al., 2016) BM-derived MSC (bmMSC) supply is the painful harvesting procedure marking their application in research and in the clinical setting limited. Over time, a number of other tissues have been identified as alternative sources for hMSC. Today, MSC can be isolated from multiple tissues (Ullah et al., 2015). The human MSC (hMSC) properties can vary greatly depending on multiple parameters including tissue source, isolation method and medium composition and several studies mentioned variations in the differentiation potential of MSC from different tissue sources. Table 1 summaries some of the currently used tissue sources and the respective confirmed differentiation potentials.  Table 3.

Mesenchymal Stem Cell Markers Co-expression:
The purity of MSCs can be increased by using more than one MSC marker for positive selection. As an example, a recent publication demonstrated that selection of mesenchymal stem cells using CD271/NGF R, CD90/Thy1, and CD106/VCAM-1 resulted in a highly clonogenic population of cells (Simmons & Torok-Storb, 1991). Specifically, the addition of CD106 as a marker for positive selection led to isolation of cells with five times greater clonogenic potential compared to the cells isolated with CD271/and CD90 alone. The degree of co expression of surface markers on MSCs also studied (Rasmusson et al., 2003

CONCLUSION:
Mesenchymal stem cells have been isolated from a wide range of species and tissues using several tech-niques. MSCs are isolated as a heterogeneous population of cells that differ in growth kinetics and differentiation potentials. A large number of markers have been brought forward to facilitate the isolation of MSCs from their surrounding environment or the selection of MSCs with high stemness. With their ability to differentiate into multiple lineages, secrete factors related to immune regulation, and migrate to-ward sites of inflammation, All these properties of MSCs make them distinct from other stem cells and can be used in future cell replacement therapy and many other clinical implications. In this review, we concisely bring up the current data available for MSCs isolation sources, characterization markers and its immunomodulatory properties. The future MSCs research should focus on finding more suitable markers to isolate the sourcespecific MSCs, basic understanding of growth regulators in differentiation and trans-differentiation and its immunomodulatory properties to modify the host immune environment.

ACKNOWLEDGEMENT:
The authors would like to express their gratitude Pakistan Council of Scientific and Industrial Research for their constructive cooperation throughout the research work.

CONFLICTS OF INTEREST:
The authors wish to confirm that there are no conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome.

REFERENCES:
1 Prospective isolation and characterization of mesenchymal stem cells from human placenta using a frizzled-9-specific monoclonal antibody.