Human Wharton's Jelly-Derived Stem Cells Display a Distinct Immunomodulatory and Proregenerative Transcriptional Signature Compared to Bone Marrow-Derived Stem Cells

Abstract

Mesenchymal stromal cells (MSCs) are multipotent stem cells with immunosuppressive and trophic support functions. While MSCs from different sources frequently display a similar appearance in culture, they often show differences in their surface marker and gene expression profiles. Although bone marrow is considered the "gold standard" tissue to isolate classical MSCs (BM-MSC), MSC-like cells are currently also derived from more easily accessible extra-embryonic tissues such as the umbilical cord. In this study, we defined the best way to isolate MSCs from the Wharton's jelly of the human umbilical cord (WJ-MSC) and assessed the mesenchymal and immunological phenotype of BM-MSC and WJ-MSC. Moreover, the gene expression profile of established WJ-MSC cultures was compared to two different bone marrow-derived stem cell populations (BM-MSC and multipotent adult progenitor cells or MAPC). We observed that explant culturing of Wharton's jelly matrix is superior to collagenase tissue digestion for obtaining mesenchymal-like cells, with explant isolated cells displaying increased expansion potential. While being phenotypically similar to adult MSCs, WJ-MSC show a different gene expression profile. Gene ontology analysis revealed that genes associated with cell adhesion, proliferation, and immune system functioning are enriched in WJ-MSC. In vivo transplantation confirms their immune modulatory effect on T cells, similar to BM-MSC and MAPC. Furthermore, WJ-MSC intrinsically overexpress genes involved in neurotrophic support and their secretome induces neuronal maturation of SH-SY5Y neuroblastoma cells to a greater extent than BM-MSC. This signature makes WJ-MSC an attractive candidate for cell-based therapy in neurodegenerative and immune-mediated central nervous system disorders such as multiple sclerosis, Parkinson's disease, or amyotrophic lateral sclerosis.

Kartogenin preconditioning commits mesenchymal stem cells to a precartilaginous stage with enhanced chondrogenic potential by modulating JNK and β‐catenin–related pathways

“…For primary culture of hUCMSCs, the tissue expiant attachment culture method was employed as previously described in Donders et al . (18). Briefly, umbilical cords were washed repeatedly to eliminate umbilical cord blood.…”

“…Human umbilical cords were collected from newborn infants delivered by cesarean section in the Department of Obstetrics and Gynecology, Shanghai First Maternity and Infant Hospital (Shanghai, China), with parental consent. For primary culture of hUCMSCs, the tissue explant attachment culture method was employed as previously described in Donders et al (18). Briefly, umbilical cords were washed repeatedly to eliminate umbilical cord blood.…”

Five Decades Later, Are Mesenchymal Stem Cells Still Relevant?

“…Donor age is an important factor affecting MSC efficacy. MSCs grown from neonatal tissues show a longer lifespan, higher proliferation rate and differentiation potential when compared to adult tissues (Donders et al, 2018). Furthermore, neonatal tissues are easily available, do not require invasive procedures for procurement and are ethically non-controversial.…”

Mesenchymal Stem Cell-Based Therapy for Cardiovascular Disease: Progress and Challenges

“…92 UCM-(Wharton's jelly) MSCs secrete higher levels of immune-signaling molecules and neurotrophic factors, such as brain-derived neurotrophic factor (BDNF), compared to BM-MSCs, suggesting a greater beneficial role for Wharton jelly-MSCs in neurodegenerative diseases. 93 Similarly, MSCs derived from embryonic stem cells (ESC-MSCs), which, like iPSC-MSCs, appear to represent an alternative source for stem cell therapy, may also better support neurogenic-related processes compared with BM-MSCs, which enhance angiogenesis in vitro 94,95 and in the damaged myocardium. 85,96,97 Furthermore, a recent clinical study by Premer et al 86 shows that allogeneic MSC therapy improves endothelial function in patients with heart disease.…”