Faculty Bibliography

Vascularized composite allograft (VCA) transplantation (also referred to as composite tissue allotransplantation) has demonstrated clinical success in cases of hand, arm and face transplantation despite prior belief that skin provides an insurmountable barrier to allograft rejection. These overall good outcomes are facilitated by substantial immunosuppressive requirements in otherwise healthy patients, yet still demonstrate frequent rejection episodes. We developed a nonhuman primate model of facial segment allotransplantation to elucidate the unique pathophysiology and immunosuppressive requirements of VCA with addition of concomitant vascularized bone marrow (VBM). Heterotopically transplanted facial segment VCA with VBM treated only with tacrolimus and mycophenolate mofetil (MMF) demonstrated prolonged rejection-free survival, compared to VCA without VBM that demonstrated early rejection episodes and graft loss. While VCA with VBM demonstrated sporadic macrochimerism, acute and chronic rejection and graft loss occurred after discontinuation of immunosuppression. These data support an immunomodulatory role of VBM in VCA that reduces immunosuppressive requirements while providing improved outcomes.

Surgical and traumatic wounds develop hypertrophic scarring when exposed to lengthwise stress. The length-control suture (LCS) technique, in which a suture is passed in a closed-loop beneath the wound and anchored to the underside of the dermis, thereby pulling the apices inward, protects wounds from these forces and also limits the formation of dog-ears. Between 2006 and 2009, a retrospective review was performed in 230 consecutive patients who underwent wound closure with the LCS technique by a single surgeon. Wounds were evaluated at 6 weeks and 6 months. In 223 cases (97%), the technique resulted in a scar that was thin, soft, and flat. There were 6 cases of spitting and 1 case of hypertrophy. The LCS technique is useful for a wide variety of surgical and traumatic wounds across all anatomic regions. This technique if used results in scars that are reliably flat, thin, and supple within 6 months.

Restoration of shoulder stability in post-traumatic plexopathy patients is very important because more distal functions depend on a stable and functioning shoulder. The purpose of this study is to present our experience with secondary surgeries in patients with devastating paralysis. Functional outcomes were analyzed in relation to age, severity score and type of reconstruction. The medical records of 55 post-traumatic plexopathy patients who underwent secondary shoulder reconstruction, by a single surgeon, between 1978 and 2006, were reviewed. 55 patients had 73 procedures, 44 for shoulder abduction and 29 for external rotation. 38 patients underwent secondary surgery to augment shoulder abduction. Trapezius advancement was performed in 14 patients, double free muscle transfer in 18, free latissimus dorsi in 4 and triceps muscle transfer in 2 patients. 26 patients had secondary procedures for enhancement of shoulder external rotation. Dynamic rerouting of latissimus dorsi and teres major was carried out in 18 patients and rotational humerus osteotomy in 11 patients. All patients had improvement of shoulder stability and function. Shoulder abduction reached 40.80 +/- 15.93 and external rotation at 24.28 +/- 17.90 degrees . Trapezius advancement yielded 41.81 +/- 9.02 degrees of abduction. Latissimus dorsi yielded stronger shoulder abduction than adductor longus. Rerouting of latissimus dorsi and teres major attained 22.33 +/- 20.31 degrees of dynamic external rotation while humerus osteotomy produced 26.87 +/- 10.32 of external rotation. Secondary procedures such as pedicle and free muscles transfers, tendon transfers, and rotational humerus osteotomy augment shoulder stability and function in patients with irreparable paralysis.

Melanocyte stem cells (McSCs) intimately interact with epithelial stem cells (EpSCs) in the hair follicle bulge and secondary hair germ (sHG). Together, they undergo activation and differentiation to regenerate pigmented hair. However, the mechanisms behind this coordinated stem cell behavior have not been elucidated. Here, we identified Wnt signaling as a key pathway that couples the behavior of the two stem cells. EpSCs and McSCs coordinately activate Wnt signaling at the onset of hair follicle regeneration within the sHG. Using genetic mouse models that specifically target either EpSCs or McSCs, we show that Wnt activation in McSCs drives their differentiation into pigment-producing melanocytes, while EpSC Wnt signaling not only dictates hair follicle formation but also regulates McSC proliferation during hair regeneration. Our data define a role for Wnt signaling in the regulation of McSCs and also illustrate a mechanism for regeneration of complex organs through collaboration between heterotypic stem cell populations. PAPERFLICK: