Biology of Stem Cells in Human Umbilical Cord Stroma: In Situ and In Vitro Surveys

Abstract

Cells in the umbilical cord stroma have gained attention in recent years; however, differentiation to certain lineages in humans has been demonstrated in few studies. Unlike bone marrow MSCs, human umbilical cord stroma cells (HUCSCs) are far from being well characterized. This study attempts to describe proliferation, structural, and differentiation properties of these cells to account for their exceptional nature in many aspects. Cellular dynamics, cellular structure, and the degree of transformations during expansion and differentiation into mesenchymal and neuronal lineages were examined in vitro over a 10-month period. Comparisons with human bone marrow MSCs regarding differentiation were performed. HUCSCs in culture revealed two distinct cell populations, type 1 and type 2 cells, that possessed differential vimentin and cytokeratin filaments. Corresponding cells were encountered in cord sections displaying region-specific localization. ␣-Smooth muscle actin and desmin filaments, which were evident in cord sections, diminished through passages. No difference was noted regarding type 1 and type 2 cells in differentiation to chondrogenic, adipogenic, and osteogenic lineages, whereas a preferential differentiation was noted in neuronal lineage. Relative success was achieved by production of chondrocytic spheres and osteogenic monolayers, whereas adipocytes were immature compared with bone marrow MSCs. The presence of neuronal markers suggests that they transform into a certain state of maturity under neurogenic induction. Conclusively, HUCSCs retain their original phenotype in culture without spontaneous differentiation, have a limited lifespan, and bear multipotent stem cell characteristics. Given these characteristics, they may be generally considered progenitor cells if manipulated under appropriate conditions and deserve further study to be potentially used in cell-based therapies. STEM CELLS 2007;25:319 -331

Development of human umbilical cord matrix stem cell-based gene therapy for experimental lung tumors

“…The properties that promote their potential utility are the large number of cells recoverable from the umbilical cord, the noninvasive harvest following birth, and the abundant supply of umbilical cords. 2,3 Thus, they may offer an immediate avenue for cytotherapy, when time is of the essence for such therapy, for example, in cases of malignant neoplasia. UCMS cells transplanted into rodent neurodegenerative models [4][5][6] have been extensively characterized 3 and they express many of the genes expressed by primitive stem cells such as embryonic stem cells (ESCs).…”

Insulin‐like growth factor‐I improves chondrogenesis of predifferentiated human umbilical cord mesenchymal stromal cells

“…2,3 Human UCMSCs (hUCMSCs) express surface markers that were identified with other mesenchymal stromal cells (MSCs) such as CD73, CD90, CD105, and are negative for hematopoietic markers such as CD34 and CD45. [4][5][6][7][8] hUCMSCs can differentiate along a variety of cell lineages that can be utilized for tissue engineering and regenerative medicine such as osteogenic, chondrogenic, myogenic, and adipogenic. [4][5][6]9,10 In chondrogenic differentiation, transforming growth factor-beta isoforms (TGF-b1, b2, and b3) are known to play an important role.…”

“…[4][5][6][7][8] hUCMSCs can differentiate along a variety of cell lineages that can be utilized for tissue engineering and regenerative medicine such as osteogenic, chondrogenic, myogenic, and adipogenic. [4][5][6]9,10 In chondrogenic differentiation, transforming growth factor-beta isoforms (TGF-b1, b2, and b3) are known to play an important role. 11 In cell pellets [4][5][6] and polyglycolic acid (PGA) scaffolds, 12,13 TGF-b1 4,12,13 or -b3 5,6 have been incorporated into serum-free media to induce chondrogenic differentiation of hUCMSCs in 2-3 weeks, which was revealed by a positive immunostaining for type II collagen [4][5][6]12,13 and aggrecan.…”

“…[4][5][6]9,10 In chondrogenic differentiation, transforming growth factor-beta isoforms (TGF-b1, b2, and b3) are known to play an important role. 11 In cell pellets [4][5][6] and polyglycolic acid (PGA) scaffolds, 12,13 TGF-b1 4,12,13 or -b3 5,6 have been incorporated into serum-free media to induce chondrogenic differentiation of hUCMSCs in 2-3 weeks, which was revealed by a positive immunostaining for type II collagen [4][5][6]12,13 and aggrecan. 12,13 Insulin-like growth factor-I (IGF-I), an important anabolic agent for several different tissues in the body, [14][15][16] has been demonstrated by most studies to have little or no effect on chondrogenic differentiation in the presence of insulin-transferrin-selenium (ITS) with MSCs, 17,18 but promoted proliferation and biosynthesis in vitro of both mature hyaline cartilage and fibrocartilage cells.…”

State of the art and future perspectives of articular cartilage regeneration: a focus on adipose-derived stem cells and platelet-derived products

“…Termed 'human umbilical cord matrix cells' (HUCM), the immature progenitor cells have been found to possess multipotent differentiation capacity, as indicated by successful transformation into adipocytes, chondrocytes, osteoblasts and myoblasts (Can and Karahuseyinoglu, 2007). A few studies focused on chondrogenic differentiation of HUCM in 3D culture, during which GAGs as well as collagen I and II were detected histologically (Bailey et al, 2007;Karahuseyinoglu et al, 2007;Wang et al, 2004Wang et al, , 2008. In contrast to BMSC and ASC, which have been demonstrated to possess the ability to synthesize hyaline-like cartilage, the expression of collagen type II and aggrecan is decreased in HUCM, indicating the synthesis of fibrous tissue (Hildner et al, 2010b;.…”