The discussion about the clinical risk of zoonoses in xenotransplantation has recently culminated in the demand for a moratorium on clinical organ transplantation using pig donors. The basis for this discussion was a recent report showing a possible trans-species transmission of pig endogenous retrovirus (PERV) by in vitro transfer to human cell lines. At present, it remains unclear if this could also happen in vivo or in the setting of xenotransplantation. Potential in vivo transfer of PERV after xenotransplantation was investigated in an experimental pig-to-baboon cell transplantation model. Baboons were immunosuppressed with highdose cyclophosphamide (total 45-150 mg/kg) and transplanted with primary porcine aortic endothelial cells (PAEC). Tissue samples (skin, lymph nodes, lung) and peripheral blood leukocytes of 15 baboons, taken about 12-24 months after transplantation of PAEC, were then analyzed by PCR and showed no PERV infection. PERV expression in PAEC was also analyzed: PERV mRNA and reverse transcriptase in the culture supernatant could be detected. In spite of the release of retroviral particles from cultured PAEC, transplantation of these cells into baboon recipients did not result in virus transmission, not even under heavy immunosuppression.
Melanoma growth stimulatory activity/gro alpha (MGSA), a member of the alpha-chemokine family, is produced by a variety of dermal and epidermal cells and can act in a paracrine and autocrine fashion. However, little is known about the importance of MGSA in wound healing. In this study, we quantified the levels of MGSA protein in burn blister and donor site wound fluids. We studied the effects of MGSA on proliferation and migration of primary human keratinocytes and modulation of their integrin expression. Blister fluids contained 0.79 ng/ml (range 0.018 to 4.86 ng/ml) MGSA. Substantial increasing amounts of MGSA were found in donor site fluids from day 1 through day 5 with mean levels ranging from 1.77 to 103 ng/ml at postoperative day 5, which correlated with increasing amounts of tumor necrosis factor alpha (r = 0.86), a known stimulus for MGSA production. In vitro proliferation experiments revealed a maximum stimulation (2.6-fold) with 10 ng/ ml MGSA for 7 days over unstimulated keratinocyte controls; the ED50 was 0.2 ng/ml. DNA content analysis revealed an increase in S phase with 10 ng/ml MGSA stimulation. In cultured keratinocytes, MGSA enhanced the mean fluorescence intensity for alpha 6, while no significant change was seen for beta 1, alpha 2 and alpha 5. We also studied the effect of topically applied MGSA (50 ng/cm2) on the healing of meshed split-thickness human skin grafts on athymic mice. In these wounds, MGSA stimulated the rate of epithelialization (P < 0.05) at day 7, and an increased proportion of mitotic keratinocytes was observed. Wound contraction was significantly (P < 0.05) reduced on days 7 and 14 in the MGSA-treated group. These results suggest that MGSA participates in wound healing by stimulating keratinocyte proliferation.
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