Bone marrow as a source of circulating CXCR4+ tissue-committed stem cells

Abstract

Several studies have suggested that adult haematopoietic stem cells (HSCs) may be capable of transdifferentiating across tissue-lineage boundaries, giving rise to the concept that these stem cells are plastic in their differentiative capacity. This topic created much excitement in the scientific community, with the prospect of employing HSCs in tissue/organ regeneration (e.g. heart infarct, stroke, liver damage) as an alternative to multipotent embryonic stem cells. However, recent observations, and several alternative explanations of previously published data (e.g. cell fusion, epigenetic changes), do not support the concept of HSC plasticity. Our recent studies, in which we employed chemotactic isolation to a stromal-cell-derived-factor-1 (SDF-1) gradient combined with real-time reverse transcriptase (RT)-PCR/immuno-histochemical analyses, revealed that bone marrow (BM) contains a highly mobile population of CXCR4+ cells that express mRNA/proteins for various markers of early tissue-committed stem cells (TCSCs). Based on this we postulate that the BM is not only a home for HSCs, but also a 'hideout' for non-haematopoietic CXCR4+ TCSCs, and we suggest that their presence in BM tissue should be considered before experimental evidence is interpreted simply as transdifferentiation/plasticity of HSCs. Furthermore, our observation that the number of TCSCs is the highest in BM of young animals and decreases with age provides a novel insight into aging, and may explain why the regeneration process becomes less effective in older individuals.