Cell therapy in dermatology

Abstract

Harnessing the regenerative capacity of keratinocytes and fibroblasts from human skin has created new opportunities to develop cell-based therapies for patients. Cultured cells and bioengineered skin products are being used to treat patients with inherited and acquired skin disorders associated with defective skin, and further clinical trials of new products are in progress. The capacity of extracutaneous sources of cells such as bone marrow is also being investigated for its plasticity in regenerating skin, and new strategies, such as the derivation of inducible pluripotent stem cells, also hold great promise for future cell therapies in dermatology. This article reviews some of the preclinical and clinical studies and future directions relating to cell therapy in dermatology, particularly for inherited skin diseases associated with fragile skin and poor wound healing.

Figure 1.

Intradermal injections of allogeneic fibroblasts promote wound healing in RDEB. A stubborn wound on the side of the neck in this 23-yr-old man with RDEB showed limited improvement and persisting erosions after skin grafting. However, 8 d after fibroblast injection there was significant healing of erosions and improved quality of life; he was able to wear a shirt without discomfort. The clinical benefits of the fibroblast injections lasted for 5–6 mo.

Figure 2.

BM cells can correct lack of C7 in RDEB mouse skin. Grafting of mouse skin lacking C7 onto a mouse with green fluorescent BM leads to some BM cells entering the epidermis and follicular epithelium. Moreover, new basement membrane C7 (red) is noted in proximity to these green cells. Scale bar, 25 µm. (This figure is based on data reported by Tamai et al. 2011.)

Figure 3.

Healing of a chronic erosion in RDEB is enhanced by intradermal injection of allogeneic MSCs. Injecting third-party BM-derived MSCs, as shown in the day 0 image (top left), leads to re-epithelialization and clinical improvement seen at day 7 and day 64. The clinical benefits were sustained for 4–6 mo. (The original images were kindly provided by Dr. Francis Palisson, based on data reported by Conget et al. 2010.)

Figure 4.

Whole BMT results in clinicopathological correction of the skin pathology in RDEB. This 15-mo-old child shows a marked improvement with healing of chronic wounds and fewer blisters 100 d after BMT. There is also increased C7 at the DEJ (arrows). Scale bar, 25 µm. (The original images were kindly provided by Dr. Jakub Tolar, based on data reported by Wagner et al. 2010.)

Figure 5.

Revertant mosaicism represents a form of natural gene therapy in RDEB skin. This 40-yr-old man with RDEB has a patch of skin on his right shin that does not blister (unlike the surrounding skin that blisters after minor trauma). Skin from the reverted area shows near-normal intensity C7 immunoreactivity at the DEJ in contrast to the complete absence of C7 in the unreverted skin. Scale bar, 25 µm. (Images are based on data reported by Almaani et al. 2010.)