Umbilical cord-derived mesenchymal stem cells (UC-MSCs) are characterized by their plastic adherence, multipotency and a standard MSC phenotype. Umbilical cord-derived MSCs exhibit a gene expression profile more similar to that of embryonic stem cells (ESCs) than of bone marrow-derived MSCs (BM-MSCs) and self-renew much faster than BM-MSCs. However, MSCs derived from bone marrow, umbilical cord arteries, vein, WJ and the UC lining membrane showed no significant immunophenotypic differences.
UC-MSCs can be derived in a noninvasive and ethically acceptable manner and substantial UC-MSC counts can be readily obtained after expansion. The umbilical cord contains two umbilical arteries (UCAs) and one umbilical vein (UCV), all of which are embedded in Wharton’s jelly (WJ), which is a mucous connective tissue, and then encased in the amniotic epithelium. UC-MSC derivation from whole UCs or from specific UC compartments is executed using either the explant or enzymatic digestion method.
There are four umbilical cord tissue-derived sources typically exploited for MSCs isolation:
Whole umbilical cord (UC-MSCs);
Compartments of umbilical cord: Wharton’s jelly (WJ-MSCs) or Umbilical vessels (UCA-MSCs and UCV-MSCs);
Umbilical cord lining and sub-amnion
Human umbilical cord perivascular stem cells (HUCPVC)
Controversy exists regarding superiority of UC-MSC isolation from whole umbilical cords, when compared to those derived from UC compartments, particularly with respect to their proliferation, differentiation and immunosuppressive capacities.
Umbilical cord-derived mesenchymal stem cells meet the minimal criteria for defining MSCs, recommended by the International Society of Cell Therapy (ISCT). Namely, they adhere to plastic, differentiate into adipocytes, chondrocytes and osteocytes and express adhesion markers such as CD29 and CD44, mesenchymal markers such as CD90, CD73 and CD105 and human leukocyte differentiation antigen class I (HLA-ABC), but not endothelial cell marker CD31, hematopoietic cell markers CD34, CD45 and CD117 and human leukocyte differentiation antigen class II (HLA-DR). UC-MSCs express low levels of ESC markers, such as Oct4, Nanog, Sox-2 and KLF4, classifying them as primitive stem cells, somewhere between ESCs and adult stem cells.
Due to the lack of expression of HLA-DR, CD80 and CD86, UC-MSCs do not evoke acute rejection and are suitable for allogeneic cell-based therapy. UC-MSCs possess immunosuppressive properties, mediated by soluble factors, such as PGE2, galectin-1 and HLA-G5, and by cell-to-cell contacts.
Umbilical cord-derived mesenchymal stem cells can be effectively utilized for therapeutic applications of various diseases