Direct Comparison of Wharton's Jelly and Bone Marrow-Derived Mesenchymal Stromal Cells to Enhance Engraftment of Cord Blood CD34⁺Transplants

Abstract

Cotransplantation of CD34+ hematopoietic stem and progenitor cells (HSPCs) with mesenchymal stromal cells (MSCs) enhances HSPC engraftment. For these applications, MSCs are mostly obtained from bone marrow (BM). However, MSCs can also be isolated from the Wharton's jelly (WJ) of the human umbilical cord. This source, regarded to be a waste product, enables a relatively low-cost MSC acquisition without any burden to the donor. In this study, we evaluated the ability of WJ MSCs to enhance HSPC engraftment. First, we compared cultured human WJ MSCs with human BM-derived MSCs (BM MSCs) for in vitro marker expression, immunomodulatory capacity, and differentiation into three mesenchymal lineages. Although we confirmed that WJ MSCs have a more restricted differentiation capacity, both WJ MSCs and BM MSCs expressed similar levels of surface markers and exhibited similar immune inhibitory capacities. Most importantly, cotransplantation of either WJ MSCs or BM MSCs with CB CD34 + cells into NOD SCID mice showed similar enhanced recovery of human platelets and CD45 + cells in the peripheral blood and a 3-fold higher engraftment in the BM, blood, and spleen 6 weeks after transplantation when compared to transplantation of CD34 + cells alone. Upon coincubation, both MSC sources increased the expression of adhesion molecules on CD34 + cells, although stromal cell-derived factor-1 (SDF-1)-induced migration of CD34 + cells remained unaltered. Interestingly, there was an increase in CFU-GEMM when CB CD34 + cells were cultured on monolayers of WJ MSCs in the presence of exogenous thrombopoietin, and an increase in BFU-E when BM MSCs replaced WJ MSCs in such cultures. Our results suggest that WJ MSC is likely to be a practical alternative for BM MSC to enhance CB CD34 + cell engraftment.

LIGHT (TNFSF14) Increases the Survival and Proliferation of Human Bone Marrow-Derived Mesenchymal Stem Cells

“…In the past decade, many basic studies showed the brilliant results of MSC-based therapeutic plans, including myocardial infarcts [32], diabetes [33], neurological disorders [5,7], and GVHD [7,12]. In addition, MSCs exhibit therapeutic potential for diverse diseases, including Osteogenesis imperfecta [10], GVHD [11–13], myocardial infarction [14,15], Crohn’s disease [16], alcoholic cirrhosis [17], and amyotrophic lateral sclerosis [18,19].…”

“…The most common method is based on the capacity of MSCs to adhere to plastic surfaces [2,33]. After 3-day culture in a humidified incubator at 37°C and 5% CO 2 , the non-adhering cells were washed from the flask using PBS.…”

Human Wharton’s jelly mesenchymal stem cells protect axotomized rat retinal ganglion cells via secretion of anti-inflammatory and neurotrophic factors

“…Besides de abovementioned advantages, hWJMSCs, have an enhanced expression of neurotrophic factors, and a spontaneous tendency toward a neural lineage differentiation compared to MSCs isolated from adult tissues 13 , 14 .…”

Umbilical cord stem cells: biological characteristics, approaches to banking and clinical application

“…Introduction of the mesenchymal stem cells belongs to important therapeutic strategies in hematologic transplantology. Adjuvant transplant of umbilical cord MSCs was shown to facilitate engraftment of the transplant of the bone marrow, peripheral and cord blood [31,32,33,34]. Due to outstanding immunosuppressive properties umbilical cord mesenchymal stem cells are also increasingly used in the treatment of the graft-versus-host disease [51].…”

“…• Availability, cost-effectiveness, ethics and simplicity of obtaining [1,4,13 [13,32,33,34]; • Effective medium for the culture of other cell populations [6,14];…”