Fan Qingyuan, Yee Carole Lee, Ohyama Manabu, Tock Christine, Zhang Guofeng, Darling Thomas N, Vogel Jonathan C
Dermatology Branch, National Cancer Institute, Office of Research Service, National Institutes of Health, Bethesda, MD 20892-1908, USA.
Exp Hematol. 2006 May;34(5):672-9. doi: 10.1016/j.exphem.2006.02.002.
Because the ability of bone marrow-derived cells (BMDCs) to repopulate tissues and the possible mechanisms of repopulation remain controversial, we used two distinct murine models to determine whether BMDCs can repopulate epidermal keratinocytes during either steady-state homeostasis or after tissue injury.
The accessibility of skin keratinocytes makes it an excellent tissue to assess BMDC repopulation. In the two murine models, BMDCs from either male homologous B6, 129S Rosa26 mice that constitutively express ss-galactosidase or male hemizygote C57 BL/6-Tg(ACTbEGFP)1Osb/J mice expressing enhanced green fluorescent protein were transplanted via tail vein injection into control lethally irradiated (9.5 Gy) congenic female recipients and the percentage of keratinocytes derived from the transplanted BMDCs, both with and without wounding, was carefully determined.
Analysis of bone marrow, thymus, spleen, and lymph nodes confirmed complete engraftment of donor BMDCs 6 months post-bone marrow transplantation. However, during steady-state homeostasis, bone marrow-derived keratinocytes could not be detected in the epidermis. In a skin wound-healing model, the epidermis contained only rare bone marrow-derived keratinocytes (< 0.0001%) but did contain scattered bone marrow-derived Langerhans cells.
These results suggest that BMDCs do not significantly contribute to steady-state epidermal homeostasis and are not required or responsible for providing keratinocyte stem cells and keratinocyte repopulation following skin injury.
由于骨髓来源细胞(BMDCs)重新填充组织的能力以及重新填充的可能机制仍存在争议,我们使用了两种不同的小鼠模型来确定BMDCs在稳态平衡期间或组织损伤后是否能够重新填充表皮角质形成细胞。
皮肤角质形成细胞易于获取,使其成为评估BMDC重新填充的理想组织。在这两种小鼠模型中,将来自组成性表达β-半乳糖苷酶的雄性同源B6、129S Rosa26小鼠或表达增强型绿色荧光蛋白的雄性半合子C57 BL/6-Tg(ACTbEGFP)1Osb/J小鼠的BMDCs通过尾静脉注射移植到经致死性照射(9.5 Gy)的同基因雌性受体中,并仔细测定有或无创伤情况下源自移植BMDCs的角质形成细胞百分比。
对骨髓、胸腺、脾脏和淋巴结的分析证实,骨髓移植后6个月供体BMDCs完全植入。然而,在稳态平衡期间,表皮中未检测到源自骨髓的角质形成细胞。在皮肤伤口愈合模型中,表皮中仅含有罕见的源自骨髓的角质形成细胞(<0.0001%),但确实含有散在的源自骨髓的朗格汉斯细胞。
这些结果表明,BMDCs对稳态表皮平衡没有显著贡献,在皮肤损伤后也不需要或不负责提供角质形成干细胞和角质形成细胞的重新填充。