Wharton’s jelly-derived mesenchymal stromal cells isolated from umbilical cord were used to recreate a human stromal environment for B-cell development in vitro. In co-culture, CD34+ hematopoietic progenitors from bone marrow or cord blood differentiated into mature IgM-expressing B cells by day 11, while the Nalm-16 B-ALL cell line showed rapid IgM expression as early as day 5. This model highlights the ability of WJ-MSC to efficiently support human B-cell differentiation and maturation in vitro.
ABSTRACT
Mesenchymal stem cells (MSC) represent the main stromal component of the bone marrow (BM) niche and are crucial to maintain hematopoietic tissue homeostasis. MSC exhibits extraordinary and multiple properties. In terms of expanding potential and differentiation capacity, Wharton jelly MSC (WJ-MSC), derived from the umbilical cord, was described as being greater and more performing than MSC from BM or other sources. WJ-MSC mimics the hematopoietic niche and supports hematopoietic stem cells (HSC) expansion ex vivo. This study aimed to evaluate the effects of human WJ-MSC cocultured with HSC in a B-cell differentiation protocol. Remarkably, results highlight WJ-MSC use as a preferable feeder layer to efficiently support HSC commitment toward the B-lineage. Over 11 days of HSC coculture with WJ-MSC, B-cell genes (E2A, RAG1, RAG2, etc.) expression patterns and B-cell markers (CD19, immunoglobulin chain, etc.) acquisition were evidenced. WJ-MSc were also able to unlock the B-lineage differentiation blockade of the acute lymphoblastic leukemia cell line Nalm16. This model might provide a new strategy to support ex vivo B-cell differentiation using the powerful properties of WJ-MSC. This study implements a new approach to improve understanding of B-leukemogenesis and B-cell acute lymphoblastic leukemia (B-ALL) pathophysiology.