Local signals in stem cell-based bone marrow regeneration.
The cellular basis of bone marrow (BM) tissue development and regeneration is mediated through hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs). Local interplays between hematopoietic cells and BM stromal cells (BMSCs) determine the reconstitution of hematopoiesis after myelosuppression. Here we review the BM local signals in control of BM regeneration after insults. Hematopoietic growth factors (HGFs) and cytokines produced by BMSCs are primary factors in regulation of BM hematopoiesis. Morphogens which are critical to early embryo development in multiple species have been added to the family of HSCs regulators, including families of Wnt proteins, Notch ligands, BMPs, and Hedgehogs. Global gene expression analysis of HSCs and BMSCs has begun to reveal signature groups of genes for both cell types. More importantly, analysis of global gene expression coupled with biochemical and biological studies of local signals during BM regeneration have strongly suggested that HGFs and cytokines may not be the primary local regulators for BM recovery, rather chemokines (SDF-1, FGF-4) and angiogenic growth factors (VEGF-A, Ang-1) play instructive roles in BM reconstitution after myelosuppression. A new direction of management of BM toxicity is emerging from the identification of BM regenerative regulators.
Han
Wei
W
Stem Cell Research Center, School of Pharmacy, Shanghai Jiao-Tong University, Shanghai 200030, China. weihan@sjtu.edu.cn
Yu
Yan
Y
Liu
Xin Yuan
XY
D001854:Bone Marrow Cells / Q000502:physiology*; D016207:Cytokines / Q000378:metabolism; D064420:Drug-Related Side Effects and Adverse Reactions; D020869:Gene Expression Profiling; D006410:Hematopoiesis / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D011878:Radiotherapy / Q000009:adverse effects; D012038:Regeneration / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D017154:Stromal Cells / Q000502:physiology
D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins