Regeneration of the entire human epidermis using transgenic stem cells

Junctional epidermolysis bullosa (JEB) is a severe and often lethal genetic disease caused by mutations in genes encoding the basement membrane component laminin-332. Surviving patients with JEB develop chronic wounds to the skin and mucosa, which impair their quality of life and lead to skin cancer. Here we show that autologous transgenic keratinocyte cultures regenerated an entire, fully functional epidermis on a seven-year-old child suffering from a devastating, lifethreatening form of JEB. The proviral integration pattern was maintained in vivo and epidermal renewal did not cause any clonal selection. Clonal tracing showed that the human epidermis is sustained not by equipotent progenitors, but by a limited number of long-lived stem cells, detected as holoclones, that can extensively self-renew in vitro and in vivo and produce progenitors that replenish terminally differentiated keratinocytes. This study provides a blueprint that can be applied to other stem cell-mediated combined ex vivo cell and gene therapies

The development and future of reconstructive and microvascular surgery of the hand.

The hand is often thought of as a key discriminator in what makes humans human. The hand is both intricate and fascinating in its design and function, allowing humans to interact with their surroundings, and each other. Due to its use in manipulation of the person's environment, injury to the hand is common. Devastating hand injuries have a profound, physical, psychological, financial and socially crippling effect on patients. Advances in operative techniques and improvements in microscopes and instruments allowed Malt &McKhann to perform the first successful arm replantation in 1962 [1]. This was followed by a myriad of autologous free flaps of varying composition, that were discovered after the mapping of the cutaneous blood circulation by Taylor and Palmer [2] and Mathes & Nahai's classification of muscle flaps [3] providing us with countless options to harvest and transfer healthy, well vascularised tissues into areas of injury. Since the late sixties, with the emerging subspecialty of microvascular reconstruction, surgeons have had the technical ability to salvage many amputated parts, even entire limbs. The measure of functional outcomemust incorporate the evaluation and severity ofthe initial injury and the subsequent reconstructive surgeries [4]