Eylert Gertraud, Dolp Reinhard, Parousis Alexandra, Cheng Richard, Auger Christopher, Holter Magdalena, Lang-Olip Ingrid, Reiner Viola, Kamolz Lars-Peter, Jeschke Marc G
Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, Canada.
Division of Plastic, Aesthetic, Reconstructive Surgery, Medical University of Graz, Graz, Austria.
Stem Cell Res Ther. 2021 Jan 25;12(1):82. doi: 10.1186/s13287-020-02131-6.
Multipotent mesenchymal stromal/stem cell (MSC) therapy is under investigation in promising (pre-)clinical trials for wound healing, which is crucial for survival; however, the optimal cell dosage remains unknown. The aim was to investigate the efficacy of different low-to-high MSC dosages incorporated in a biodegradable collagen-based dermal regeneration template (DRT) Integra®.
We conducted a porcine study (N = 8 Yorkshire pigs) and seeded between 200 and 2,000,000 cells/cm of umbilical cord mesenchymal stromal/stem cells on the DRT and grafted it onto full-thickness burn excised wounds. On day 28, comparisons were made between the different low-to-high cell dose groups, the acellular control, a burn wound, and healthy skin.
We found that the low dose range between 200 and 40,000 cells/cm regenerates the full-thickness burn excised wounds most efficaciously, followed by the middle dose range of 200,000-400,000 cells/cm and a high dose of 2,000,000 cells/cm. The low dose of 40,000 cells/cm accelerated reepithelialization, reduced scarring, regenerated epidermal thickness superiorly, enhanced neovascularization, reduced fibrosis, and reduced type 1 and type 2 macrophages compared to other cell dosages and the acellular control.
This regenerative cell therapy study using MSCs shows efficacy toward a low dose, which changes the paradigm that more cells lead to better wound healing outcome.
多能间充质基质/干细胞（MSC）疗法正在有前景的（临床前）临床试验中接受研究，用于伤口愈合，这对生存至关重要；然而，最佳细胞剂量仍不清楚。目的是研究不同低至高剂量的MSC掺入可生物降解的基于胶原蛋白的真皮再生模板（DRT）Integra®中的疗效。
我们进行了一项猪研究（N = 8只约克夏猪），将200至2,000,000个脐带间充质基质/干细胞/cm接种到DRT上，并将其移植到全层烧伤切除伤口上。在第28天，对不同低至高细胞剂量组、无细胞对照组、烧伤伤口和健康皮肤进行比较。
我们发现，200至40,000个细胞/cm的低剂量范围最有效地再生了全层烧伤切除伤口，其次是200,000 - 400,000个细胞/cm的中剂量范围和2,000,000个细胞/cm的高剂量。与其他细胞剂量和无细胞对照组相比，40,000个细胞/cm的低剂量加速了再上皮化，减少了瘢痕形成，更好地再生了表皮厚度，增强了新血管形成，减少了纤维化，并减少了1型和2型巨噬细胞。
这项使用MSC的再生细胞疗法研究显示低剂量具有疗效，这改变了细胞越多伤口愈合效果越好的模式。
