Mesenchymal stem cells from the Wharton's jelly of umbilical cord segments provide stromal support for the maintenance of cord blood hematopoietic stem cells during long‐term ex vivo culture

Abstract

BACKGROUND Hematopoietic stem cells (HSCs) are routinely obtained from marrow, mobilized peripheral blood, and umbilical cord blood. Mesenchymal stem cells (MSCs) are traditionally isolated from marrow. Bone marrow–derived MSCs (BM-MSCs) have previously demonstrated their ability to act as a feeder layer in support of ex vivo cord blood expansion. However, the use of BM-MSCs to support the growth, differentiation, and engraftment of cord blood may not be ideal for transplant purposes. Therefore, the potential of MSCs from a novel source, the Wharton’s jelly of umbilical cords, to act as stromal support for the long-term culture of cord blood HSC was evaluated. STUDY DESIGN AND METHODS Umbilical cord–derived MSCs (UC-MSCs) were cultured from the Wharton’s jelly of umbilical cord segments. The UC-MSCs were then profiled for expression of 12 cell surface receptors and tested for their ability to support cord blood HSCs in a long-term culture-initiating cell (LTC-IC) assay. RESULTS Upon culture, UC-MSCs express a defined set of cell surface markers (CD29, CD44, CD73, CD90, CD105, CD166, and HLA-A) and lack other markers (CD45, CD34, CD38, CD117, and HLA-DR) similar to BM-MSCs. Like BM-MSCs, UC-MSCs effectively support the growth of CD34+ cord blood cells in LTC-IC assays. CONCLUSION These data suggest the potential therapeutic application of Wharton’s jelly–derived UC-MSCs to provide stromal support structure for the long-term culture of cord blood HSCs as well as the possibility of cotransplantation of genetically identical, HLA-matched, or unmatched cord blood HSCs and UC-MSCs in the setting of HSC transplantation.

Exploring the Human Term Placenta as a Novel Source for Stem Cells and their Application in the Clinic

“…However, MSC have also been shown to be effective when sourced from other tissues including human placenta , umbilical cord (Bakhshi et al, 2008, Huang et al, 2007, Wang et al, 2004 and adipose tissue (Nakao et al, 2010). Recent papers have demonstrated that many of the specific cell-cell interactions between HSC and stromal cells are critical and may be essential for HSC regulation both in vivo (Steiner et al, 2009) and in vitro (Jing et al, 2010, Song et al, 2010, Wagner et al, 2008, Wagner et al, 2007, Wein et al, 2010.…”

Phenotype and Differentiation Potential of Stromal Populations Obtained from Various Zones of Human Umbilical Cord: An Overview

“…They have been successfully used in animal models for increasing angiogenesis in brain ischemia [44], inducing liver regeneration after hepatectomia [3], and replacing neuronal elements in Parkinson's models [42]. Moreover, MSCs from Wharton's jelly, like BMMSCs, are able to support hematopoietic stem cell proliferation [46] and increase the engrafment of these cells in NOD-SCID mice [45]. Recently, their potential use for cancer cytotherapy has been suggested [90].…”

“…Overall, cells from Wharton's jelly fit with the minimal criteria for MSCs. Nevertheless, Kadam et al, [52] have not found any expression of CD105, while Bakshi et al, [46] n.r. [36] have observed that this marker is missing in cultures of earlier passages but is present at the 5th passage.…”

“…Indeed, they support the growth and the maintenance of hematopoietic stem cells from UC blood (UCB) through the production of hematopoietic growth factors [45,46]. Consistent with their immunomodulatory properties [5], they also enhance human hematopoietic engraftment in SCID mice when co-transplanted with hematopoietic stem cells [45].…”

Ex Vivo Expansion of Cord Blood

“…Unfortunately, UCB and mobilized peripheral blood are poor sources of MSCs, 105 although a recent study did suggest that MSCs from the Wharton's jelly of umbilical cords showed surface receptors similar to other MSCs, and may be able to support UCB expansion. 106 Co-culture of UCB with MSCs (even allogeneic) can restore some of the interaction that occurs between the microenvironment of the marrow stroma and the HSC. [80][81][82][83][84] The foci of hematopoiesis and cobblestone areas are visible during coculture, 92 showing that direct HSC-MSC interactions are occurring and that the MSCs are not simply acting as a feeder layer.…”