Abstract

Human mesenchymal stem cells (MSCs) are a promising candidate for cell-based transplantation and regenerative medicine therapies. Thus in the present study Wharton’s Jelly Mesenchymal Stem Cells (WJ-MSCs) have been derived from extra embryonic umbilical cord matrix following removal of both arteries and vein. Also, to overcome the clinical limitations posed by fetal bovine serum (FBS) supplementation because of xenogeneic origin of FBS, usual FBS cell culture supplement has been replaced with human platelet lysate (HPL). Apart from general characteristic features of bone marrow-derived MSCs, wharton jelly-derived MSCs have the ability to maintain phenotypic attributes, cell growth kinetics, cell cycle pattern, in vitro multilineage differentiation plasticity, apoptotic pattern, normal karyotype-like intrinsic mesenchymal stem cell properties in long-term in vitro cultures. Moreover, the WJ-MSCs exhibited the in vitro multilineage differentiation capacity by giving rise to differentiated cells of not only mesodermal lineage but also to the cells of ectodermal and endodermal lineage. Also, WJ-MSC did not present any aberrant cell state upon in vivo transplantation in SCID mice and in vitro soft agar assays. The immunomodulatory potential assessed by gene expression levels of immunomodulatory factors upon exposure to inflammatory cytokines in the fetal WJ-MSCs was relatively higher compared to adult bone marrow-derived MSCs. WJ-MSCs seeded on decellularized amniotic membrane scaffold transplantation on the skin injury of SCID mice model demonstrates that combination of WJ-MSCs and decellularized amniotic membrane scaffold exhibited significantly better wound-healing capabilities, having reduced scar formation with hair growth and improved biomechanical properties of regenerated skin compared to WJ-MSCs alone. Further, our experimental data indicate that indocyanin green (ICG) at optimal concentration can be resourcefully used for labeling of stem cells and in vivo tracking by near infrared fluorescence non-invasive live cell imaging of labelled transplanted cells, thus proving its utility for therapeutic applications.

Highlights

  • Mesenchymal stromal cells (MSCs) are a pluripotent class of stem cells that has the ability to self-renew and differentiate into multiple cell lineages

  • The Mesenchymal stromal cells from extra embryonic tissues is an ideal choice for mesenchymal stem cells, as it can overcome the proliferative limitation posed by adult MSCs

  • The results suggest that the endogenous pluripotency marker, Nanog and SOX2 levels were significantly higher in fetal Wharton’s Jelly Mesenchymal Stem Cells (WJ-MSCs) compared to adult bone marrow derived MSCs

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Summary

Introduction

Mesenchymal stromal cells (MSCs) are a pluripotent class of stem cells that has the ability to self-renew and differentiate into multiple cell lineages. The mesenchymal stromal cells can be broadly classified into two categories; MSCs derived from adult tissues such as bone marrow, adipose tissue [2] and fetal/perinatal tissues derived such as placenta [3], umbilical cord wharton’s jelly [4], amniotic membrane etc.[5]. The Mesenchymal stromal cells from extra embryonic tissues is an ideal choice for mesenchymal stem cells, as it can overcome the proliferative limitation posed by adult MSCs. Further, fetal MSCs has proliferation capacity, ease of scalability, differentiation plasticity and exhibits some of the gene expression characteristic features of embryonic stem cells without any tumorigenicity. McElreavey et al, [9] in 1991 first isolated the mesenchymal stromal cells from wharton’s jelly portion of the umbilical cord. Auxiliary reports suggest that paracrine factors secreted by the MSCs play a very vital role in therapeutic, immunomodulatory and tissue regeneration capabilities of MSCs [18]

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