The Therapeutic Potential, Challenges and Future Clinical Directions of Stem Cells from the Wharton’s Jelly of the Human Umbilical Cord

Abstract

Mesenchymal stem cells (MSCs) from bone marrow, adult organs and fetuses face the disadvantages of invasive isolation, limited cell numbers and ethical constraints while embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) face the clinical hurdles of potential immunorejection and tumorigenesis respectively. These challenges have prompted interest in the study and evaluation of stem cells from birth-associated tissues. The umbilical cord (UC) has been the most popular. Hematopoietic stem cells (HSCs) harvested from cord blood have been successfully used for the treatment of hematopoietic diseases. Stem cell populations have also been reported in other compartments of the UC viz., amnion, subamnion, perivascular region, Wharton's jelly, umbilical blood vessel adventia and endothelium. Differences in stemness characteristics between compartments have been reported and hence derivation protocols using whole UC pieces containing all compartments yield mixed stem cell populations with varied characteristics. Stem cells derived directly from the uncontaminated Wharton's jelly (hWJSCs) appear to offer the best clinical utility because of their unique beneficial properties. They are non-controversial, can be harvested painlessly in abundance, proliferative, possess stemness properties that last several passages in vitro, multipotent, hypoimmunogenic and do not induce tumorigenesis even though they have some ESC markers. hWJSCs and its extracts (conditioned medium and lysate) also possess anti-cancer properties and support HSC expansion ex vivo. They are thus attractive autologous or allogeneic agents for the treatment of malignant and non-malignant hematopoietic and non-hematopoietic diseases. This review critically evaluates their therapeutic value, the challenges and future directions for their clinical application.

Unique Features and Clinical Application Prospect of Human Umbilical Cord Mesenchymal Stem Cells

“…Firstly, hUC-MSCs showed lower expression of CD106 and HLA-DR in comparison with BM-MSCs, but were strongly positive for surface markers such as CD13, CD44, CD90, and CD166. This profile indicated hypoimmunogeic properties of hUC-MSCs favor for allogeneic cell-based therapy [13,20,23,24] . Secondly, the proliferation analysis showed strong proliferative ability of hUCMSCs.…”

“…Secondly, the proliferation analysis showed strong proliferative ability of hUCMSCs. Compared with BM-MSCs, hUC-MSCs reached a faster population doubling time and such proliferation characteristics kept for almost 30 passages [10,13,25] .…”

“…In additional, hUC-MSCs shared most of the features with MSC from bone marrow, including their morphology and biological characteristics [10] . A great quantity of evidence showed that hUC-MSCs have great potential for self-renewal and multipotential differentiation, which can be differentiated into osteogenic cells, adipogenic cells, neural cells, cartilage cells and others under specific induction of certain factors or stimulation [12][13][14] .…”

Functional recovery after acute intravenous administration of human umbilical cord mesenchymal stem cells in rats with cerebral ischemia-reperfusion injury

“…Mesenchymal stem cells (MSCs) have emerged as a leading candidate source for stroke management; MSCs are easily obtained from a range of tissues (7), can be rapidly expanded in vitro while maintaining their potential to differentiate into multiple tissues, and are immune-privileged, with reduced risk of rejection (8). MSCs isolated from Wharton's jelly of human umbilical cords (HUMSCs) can escape immune surveillance possibly because of the absence of the major histocompatibility complex II antigen and co-stimulatory surface antigens CD40, CD80, and CD86 (9,10).…”

Proliferation, Stemness and Cardiac Differentiation Properties of Umbilical Cord Wharton^|^rsquo;s Jelly-derived Mesenchymal Stem Cells during the Continuous Passages

“…Moreover, WJ MSCs express several embryonic stem cell (ESC) markers, including Oct3/4, Nanog, SSEA-4, Sox2, Tra-1-60, alkaline phosphatase, etc. 12) . And it has been reported that when WJ MSCs are treated with 5-azacytidine (5-aza) they exhibit the cardiomyocyte phenotype and express the conventional markers for cardiac differentiation 13) for cardiac tissue regeneration in the future.…”