Chan W Y, Kohsaka S, Rezaie P
Department of Anatomy, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.
Brain Res Rev. 2007 Feb;53(2):344-54. doi: 10.1016/j.brainresrev.2006.11.002. Epub 2006 Dec 26.
Despite intense study, the precise origin and cell lineage of microglia, the resident mononuclear phagocytes of the nervous system, are still a matter for debate. Unlike macroglia (astrocytes and oligodendrocytes) and neurons, which are derived from neuroectoderm, microglial progenitors arise from peripheral mesodermal (myeloid) tissue. The view still commonly held is that tissue-resident mononuclear phagocytes (including microglia) are derived from circulating blood monocytes and these take up residence late in gestation and postnatally. However, microglial progenitors colonise the nervous system primarily during embryonic and fetal periods of development. Recent evidence indicates differences between the lineage of mononuclear phagocytes during the embryonic and fetal period from that in the neonate and adult-mononuclear phagocytes that take up residence within tissues are derived from a lineage of myeloid cells that is independent of the monocyte lineage. Our own findings on the development and differentiation of microglial progenitors, taken together with findings by other investigators, and in the context of the heterogeneity between myeloid differentiation in the fetus and in the adult, support the view that microglia are derived prenatally from mesodermal progenitors that are distinct from monocytes. Furthermore, microglial progenitors colonise the nervous system via extravascular routes initially. These findings challenge the concept that resident microglia in the nervous system are derived from circulating blood monocytes. Work is still underway to establish the tissue of origin and lineage of microglial progenitors in vivo. This information is critical not only from a developmental perspective, but significantly from a therapeutic viewpoint, as (i) the unique property of microglial progenitors to colonise the nervous system from the periphery allows these cells to be exploited as a biological and non-invasive means for cell therapy by delivering genes to the nervous system (microglial engraftment), and (ii) there are indications that microglial progenitors are specifically able to home to the nervous system. Use of microglial progenitors for therapeutic purposes becomes feasible only if the origin and cell lineage of these microglial progenitors are known and these cells can be isolated and manipulated in vitro (i.e., to express specific trophic factors) prior to therapeutic transfer (e.g., intravenously) in vivo. In this paper, we shall briefly consider the existing concepts on the origin and lineage of microglial progenitors and discuss new hypotheses in the light of emerging data that suggest clear differences between fetal and adult ontogeny of myeloid cells.
尽管进行了深入研究，但小胶质细胞（神经系统中的常驻单核吞噬细胞）的确切起源和细胞谱系仍存在争议。与源自神经外胚层的大胶质细胞（星形胶质细胞和少突胶质细胞）和神经元不同，小胶质细胞祖细胞源自外周中胚层（髓样）组织。目前仍普遍认为，组织驻留单核吞噬细胞（包括小胶质细胞）源自循环血液中的单核细胞，这些单核细胞在妊娠后期和出生后定居。然而，小胶质细胞祖细胞主要在胚胎和胎儿发育阶段定殖于神经系统。最近的证据表明，胚胎期和胎儿期的单核吞噬细胞谱系与新生儿和成年期的不同——组织内定居的单核吞噬细胞源自独立于单核细胞谱系的髓样细胞谱系。我们自己关于小胶质细胞祖细胞发育和分化的研究结果，与其他研究者的发现相结合，并结合胎儿和成人髓样分化的异质性，支持了小胶质细胞在产前源自与单核细胞不同的中胚层祖细胞的观点。此外，小胶质细胞祖细胞最初通过血管外途径定殖于神经系统。这些发现挑战了神经系统中驻留小胶质细胞源自循环血液单核细胞的概念。目前仍在努力确定小胶质细胞祖细胞在体内的起源组织和谱系。这些信息不仅从发育角度来看至关重要，而且从治疗角度来看意义重大，原因如下：（i）小胶质细胞祖细胞从外周定殖于神经系统的独特特性，使得这些细胞可以通过向神经系统递送基因（小胶质细胞植入），作为一种生物且非侵入性的细胞治疗手段加以利用；（ii）有迹象表明小胶质细胞祖细胞具有特异性归巢至神经系统的能力。只有在了解这些小胶质细胞祖细胞的起源和细胞谱系，并且能够在体外分离和操作这些细胞（即表达特定的营养因子），然后在体内进行治疗性转移（例如静脉注射）之前，将小胶质细胞祖细胞用于治疗目的才可行。在本文中，我们将简要考虑关于小胶质细胞祖细胞起源和谱系的现有概念，并根据新出现的数据讨论新的假说，这些数据表明胎儿和成人髓样细胞个体发生存在明显差异。
