Bone marrow transplants are critical to treating a number of blood diseases. The key components of these transplants are hematopoietic stem cells, or HSCs, which produce red and white blood cells. Unfortunately, bone marrow donors are limited in numbers and are often not good matches for ethnic minorities. New research published in Nature from the lab of Shahin Rafii, MD, at Weill Cornell Medical College, demonstrates a possible solution. Researchers have attempted to produce HSCs in the lab for many years, but the cells do not expand well or fail to engraft. Taking cues from normal development, Dr. Rafii’s group started with endothelial cells from the human umbilical veins or adult human blood vessels and used four transcription factors to convert them into HSC-like cells. However, based on previous research, the group reasoned that the environment, or niche, supporting these cells was instrumental in instructing and maintaining their fate. To mimic the in vivo environment, or natural developmental niche, of HSCs, they cultured the reprogrammed cells on a vascular bed derived from engineered endothelial cells that produce the proper environmental cues. Indeed, this seemed to do the trick; these vascular niche cells enable the reprogrammed cells to give rise to blood cells that expanded in culture, expressed appropriate markers, and could engraft serially into mice and produce a variety of human blood cells. This new approach will help pave the way for production of autologous (self) HSCs for transplant to treat acquired or genetic blood disorders. Research in Dr. Rafii’s lab is supported by NYSTEM grants C026878 (Institutional Training), C024180 (Shared Facility), C026438 (IIRP), C028117 (IIRP).
Sandler VM, Lis R, Liu Y, Kedem A, James D, Elemento I, Butler J, Scandura J, Rafii S. Reprogramming human endothelial cells to haematopoietic cells requires vascular induction. Nature. 2014 Jul 17;511(7509):312-8.