Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, Massachusetts, USA.
Department of Dermatology, Harvard Medical School, Boston, Massachusetts, USA.
FASEB J. 2024 Aug 15;38(15):e23873. doi: 10.1096/fj.202400866R.
For patients with lower limb amputations, prostheses are immensely helpful for mobility and the ability to perform job-related or recreational activities. However, the skin covering the amputation stump is typically transposed from adjacent areas of the leg and lacks the weight-bearing capacity that is only found in the specialized skin covering the palms and soles (a.k.a. volar skin). As a result, the skin tissue in direct contact with the prosthesis frequently breaks down, leading to the development of painful sores and other complications that limit, and often preclude, the use of prostheses. Transplanting volar skin onto amputation stumps could be a solution to these problems, but traditional skin transplantation techniques cause substantial morbidity at the donor site, such as pain and scarring, which are especially problematic for volar skin given the critical functional importance of the volar skin areas. We previously developed the technology to collect and engraft full-thickness skin tissue while avoiding long-term donor site morbidity, by harvesting the skin in the form of small (~0.5 mm diameter) cores that we termed "micro skin tissue columns" (MSTCs), so that each donor wound is small enough to heal quickly and without clinically appreciable scarring or other long-term abnormalities. The goal of this study was to establish whether a similar approach could be used to confer the structural and molecular characteristics of volar skin ectopically to other skin areas. In a human-to-mouse xenograft model, we show the long-term persistence of various human plantar MSTC-derived cell types in the murine recipient. Then in an autologous porcine model, we harvested MSTCs from the bottom of the foot and transplanted them onto excision wounds on the animals' trunks. The healing processes at both the donor and graft sites were monitored over 8 weeks, and tissue samples were taken to verify volar-specific characteristics by histology and immunohistochemistry. The volar donor sites were well-tolerated, healed rapidly, and showed no signs of scarring or any other long-term defects. The graft sites were able to maintain volar-specific histologic features and expression of characteristics protein markers, up to the 8-week duration of this study. These results suggest that MSTC grafting could be a practical approach to obtain autologous donor volar skin tissue, confer volar skin characteristics ectopically to nonvolar skin areas, improve the load-bearing capacity of amputation stump skin, and ultimately enhance mobility and quality-of-life for lower limb amputees.
对于下肢截肢患者来说,假肢在移动和进行与工作相关或娱乐活动方面非常有帮助。然而,覆盖截肢残端的皮肤通常是从腿部的相邻区域移植过来的,缺乏手掌和脚底(也称为掌侧皮肤)特有的承重能力。因此,与假肢直接接触的皮肤组织经常会破裂,导致疼痛性溃疡等并发症的发生,这些并发症限制了假肢的使用,甚至使其无法使用。将掌侧皮肤移植到截肢残端上可能是解决这些问题的一种方法,但是传统的皮肤移植技术会导致供体部位出现大量的发病率,例如疼痛和疤痕,对于掌侧皮肤来说,这些问题尤其严重,因为掌侧皮肤区域对于功能至关重要。我们之前开发了一种技术,可以通过采集小 (~0.5 毫米直径) 的“微皮肤组织柱” (MSTC) 来收集和移植全层皮肤组织,同时避免长期供体部位发病率,从而避免长期供体部位发病率,这样每个供体伤口都足够小,可以快速愈合,并且不会出现临床上明显的疤痕或其他长期异常。本研究的目的是确定是否可以采用类似的方法将掌侧皮肤的结构和分子特征异位赋予其他皮肤区域。在人-鼠异种移植模型中,我们展示了各种源自人足底 MSTC 的细胞类型在小鼠受体中的长期存在。然后,在自体猪模型中,我们从脚底采集 MSTC 并将其移植到动物躯干上的切除伤口上。在 8 周的时间里,监测供体和移植物部位的愈合过程,并通过组织学和免疫组织化学取组织样本以验证掌侧特异性特征。掌侧供体部位耐受性良好,愈合迅速,没有疤痕或任何其他长期缺陷的迹象。移植物部位能够维持掌侧特异性组织学特征和特征蛋白标志物的表达,直至本研究的 8 周持续时间。这些结果表明,MSTC 移植可能是一种实用的方法,可以获得自体供体掌侧皮肤组织,将掌侧皮肤特征异位赋予非掌侧皮肤区域,提高截肢残端皮肤的承重能力,最终提高下肢截肢患者的活动能力和生活质量。