Retinal degenerative diseases, which include inherited conditions such as retinitis pigmentosa¹ and acquired conditions such as age-related macular degeneration,² can induce significant vision loss and dramatically impact the quality of life of affected patients. The loss of light-responsive photoreceptors and the underlying nutrient-supplying retinal pigment epithelium (RPE) represent common endpoints for retinal degeneration independent of the etiology. The replacement of photoreceptors and RPE with pluripotent stem cell derivatives represents an exciting treatment strategy, which has been buoyed by the generation of three-dimensional embryonic stem cell (ESC)-derived retinal organoids that closely follow in vivo retinogenesis, exhibit a typical laminated retinal structure, and harbor elevated numbers of photoreceptors and other crucial retinal cells.^{3, 4} Current research aims in this quickly advancing field include achiving a more in-depth understanding of how stem cell-derived photoreceptors integrate into the degenerated retina and establish synaptic contacts with surrounding cells and identifying optimal cell isolation and surgical parameters that will support the success of cell transplantation strategies in the retina. In our first Featured Article published this month in STEM CELLS, Zerti et al assess the engraftment and restoration of light responses following the transplantation of human ESC (hESC)-derived cone photoreceptor precursor cells in a mouse model of retinitis pigmentosa.⁵ In a Related Article published recently in STEM CELLS Translational Medicine, Scruggs et al sought to define the optimal conditions for the preparation and subretinal transplantation of induced pluripotent stem cell (iPSC)-derived retinal precursor cells in the hope of improving the treatment of retinal degenerative diseases.⁶

Biallelic mutations in the COL7A1 gene encoding type VII collagen (or C7) can prompt the onset of recessive dystrophic epidermolysis bullosa (RDEB). This devastating inherited mucocutaneous disease disrupts the interaction of the dermal and epidermal layers that maintain barrier function and prompt the onset of painful blisters of the skin, esophagus, and gastrointestinal and genitourinary tracts.⁷ RDEB patients also suffer from an elevated risk of aggressive cutaneous squamous cell carcinoma development, which suffers from an extremely poor prognosis. Type VII collagen, an essential basement membrane protein that supports skin integrity, typically induces successful wound healing through a range of mechanisms, including keratinocyte re-epithelization, dermal fibroblast migration, and cytokine production regulation.⁸ Stem cell-based strategies, such as bone marrow (BM) transplants or intradermal injections of mesenchymal stem cells (MSCs), have shown promise as treatment options,^{9, 10} likely functioning through the homing of donor cells to the affected tissue, where they engraft and deposit functional type VII collagen. In our second Featured Article published this month in STEM CELLS, Riedl et al report that increased homing and engraftment underpin the therapeutic efficacy of a population of dermal MSCs isolated based on the expression of a specific ATP-binding cassette transporter protein in a mouse model of RDEB.¹¹ In a Related Article published recently in STEM CELLS Translational Medicine, Liao et al demonstrated that human placental-derived stem cell therapy could alleviate symptoms and extend lifespan in an RDEB model by migrating and integrating within the skin and gastrointestinal tract where they may replace lost type VII collagen.¹²

视网膜退行性疾病，包括遗传性疾病，如色素性视网膜炎¹和获得性疾病，如年龄相关性黄斑变性，²可导致显着的视力丧失并显着影响受影响患者的生活质量。光响应性光感受器的丧失和潜在的营养供应视网膜色素上皮 (RPE) 代表了与病因无关的视网膜变性的常见终点。用多能干细胞衍生物替代光感受器和 RPE 代表了一种令人兴奋的治疗策略，该策略受到密切关注体内视网膜生成的三维胚胎干细胞 (ESC) 衍生的视网膜类器官的支持，显示出典型的层状视网膜结构，并含有数量增加的光感受器和其他重要的视网膜细胞。^3、4当前在这个快速发展领域的研究目标包括更深入地了解干细胞衍生的光感受器如何整合到退化的视网膜中并与周围细胞建立突触接触，并确定最佳的细胞分离和手术参数，以支持细胞的成功。视网膜移植策略。在我们本月在STEM CELLS 上发表的第一篇专题文章中，Zerti 等人评估了在视网膜色素变性小鼠模型中移植人 ESC (hESC) 衍生的视锥光感受器前体细胞后光反应的植入和恢复。⁵在最近发表在STEM CELLS Translational Medicine 上的相关文章中，Scruggs 等人试图确定诱导多能干细胞 (iPSC) 衍生的视网膜前体细胞的制备和视网膜下移植的最佳条件，以期改善视网膜退行性疾病的治疗。⁶

在双等位基因突变COL7A1 VII基因编码类型胶原（或C7）可以提示隐性营养不良性表皮松解症（RDEB）的发作。这种破坏性的遗传性皮肤黏膜疾病破坏了维持屏障功能的真皮层和表皮层的相互作用，并促使皮肤、食道、胃肠道和泌尿生殖道出现疼痛性水疱。⁷RDEB 患者还患有侵袭性皮肤鳞状细胞癌发展的风险升高，其预后极差。VII 型胶原蛋白是一种支持皮肤完整性的必需基底膜蛋白，通常通过一系列机制诱导成功的伤口愈合，包括角质形成细胞再上皮、真皮成纤维细胞迁移和细胞因子产生调节。⁸基于干细胞的策略，例如骨髓 (BM) 移植或皮内注射间充质干细胞 (MSC)，已显示出作为治疗选择的前景，^{9, 10}可能通过供体细胞归巢到受影响的组织发挥作用，其中它们移植和沉积功能性 VII 型胶原蛋白。在我们本月发表的第二篇精选文章中干细胞、Riedl 等人报告说，增加的归巢和移植巩固了基于特定 ATP 结合盒转运蛋白在 RDEB 小鼠模型中的表达分离的真皮 MSC 群体的治疗功效。¹¹在最近发表在STEM CELLS Translational Medicine 上的一篇相关文章中，Liao 等人证明，人类胎盘干细胞疗法可以通过在皮肤和胃肠道内迁移和整合来缓解症状并延长 RDEB 模型的寿命，在那里它们可以替代丢失的VII型胶原蛋白。¹²