Are bone marrow stem cells plastic or heterogenous—That is the question

The concept that bone marrow (BM) may contain heterogeneous populations of stem cells was surprisingly not taken carefully enough into consideration in several recently reported experiments demonstrating so-called plasticity or trans-dedifferentiation of hematopoietic stem cells (HSC). These studies, without including proper controls to exclude this possibility, often lead to wrong interpretations. Accumulated evidence suggests that in addition to hematopoietic stem cells (HSC), bone marrow (BM) also harbors versatile subpopulations of tissue-committed stem cells (TCSC) and perhaps even more primitive pluripotent stem cells (PSC), and that these rare cells accumulate in bone marrow during ontogenesis, and being a mobile population of cells are released from BM into peripheral blood after tissue injury to regenerate damaged organs. Thus, the presence of TCSC/PSC in BM tissue should be considered before experimental evidence is interpreted simply as trans-dedifferentiation/plasticity of HSC. In this review, we will discuss this alternative explanation of plasticity of HSC, providing data from others and our laboratory that supports the concept that BM-derived stem cells are heterogeneous.