Rehabilitation Medicine Research Center, Mayo Clinic, Rochester, MN 55905, USA; Center for Advanced Orthopaedic Studies, BIDMC, Boston, MA 02215, USA.
Rehabilitation Medicine Research Center, Mayo Clinic, Rochester, MN 55905, USA.
Mol Ther. 2018 Jan 3;26(1):208-218. doi: 10.1016/j.ymthe.2017.10.001. Epub 2017 Oct 5.
Because muscle contains osteoprogenitor cells and has a propensity to form bone, we have explored its utility in healing large osseous defects. Healing is achieved by the insertion of muscle fragments transduced with adenovirus encoding BMP-2 (Ad.BMP-2). However, it is not known whether the genetically modified muscle contributes osteoprogenitor cells to healing defects or merely serves as a local source of BMP-2. This question is part of the larger debate on the fate of progenitor cells introduced into sites of tissue damage to promote regeneration. To address this issue, we harvested fragments of muscle from rats constitutively expressing GFP, transduced them with Ad.BMP-2, and implanted them into femoral defects in wild-type rats under various conditions. GFP cells persisted within defects for the entire 8 weeks of the experiments. In the absence of bone formation, these cells presented as fibroblasts. When bone was formed, GFP cells were present as osteoblasts and osteocytes and also among the lining cells of new blood vessels. The genetically modified muscle thus contributed progenitor cells as well as BMP-2 to the healing defect, a property of great significance in light of the extensive damage to soft tissue and consequent loss of endogenous progenitors in problematic fractures.
由于肌肉含有成骨前体细胞，并且有形成骨的倾向，我们已经探索了其在治疗大的骨缺损中的应用。通过插入转导有编码 BMP-2 的腺病毒（Ad.BMP-2）的肌肉片段来实现愈合。然而，目前尚不清楚经过基因修饰的肌肉是否为愈合缺陷提供成骨前体细胞，还是仅仅作为 BMP-2 的局部来源。这个问题是关于引入组织损伤部位以促进再生的祖细胞命运的更大争论的一部分。为了解决这个问题，我们从持续表达 GFP 的大鼠中采集肌肉片段，用 Ad.BMP-2 转导它们，并在各种条件下将它们植入野生型大鼠的股骨缺损中。GFP 细胞在整个 8 周的实验过程中都存在于缺陷中。在没有骨形成的情况下，这些细胞呈现为成纤维细胞。当形成骨时，GFP 细胞存在为成骨细胞和骨细胞，并且也存在于新血管的衬里细胞中。因此，经过基因修饰的肌肉不仅为愈合缺陷提供了 BMP-2，还提供了祖细胞，这在有问题的骨折中软组织广泛损伤和随之而来的内源性祖细胞丧失的情况下具有重要意义。
