Evangelos Badiavas

Participation of bone marrow derived cells in cutaneous wound healing

Bone marrow has long been known to be a source of stem cells capable of regeneration of the hematopoeitic system. Recent reports, however, have indicated that bone marrow might also contain early stem cells that can differentiate into other organ tissues such as skin. While these studies have illustrated that bone marrow stem cells could find their way to the skin, they have not addressed the dynamics of how bone marrow stem cells might participate in the homeostatis and regeneration of skin. In this report we followed green fluorescent protein (GFP) labeled bone marrow transplanted into non‐GFP mice in order to determine the participation of bone marrow stem cells in cutaneous wounds. Our results indicate that there are a significant number of bone marrow cells that traffic through both wounded and non‐wounded skin. Wounding stimulated the engraftment of bone marrow cells to the skin and induced bone marrow derived cells to incorporate into and differentiate into non‐hematopoietic skin structures. This report thus illustrates that bone marrow might be a valuable source of stem cells for the skin and possibly other organs. Wounding could be a stimulus for bone marrow derived stem cells to travel to organs and aid in the regeneration of damaged tissue.

Significance of N-methyl-D-aspartate (NMDA) receptor-mediated signaling in human keratinocytes

Increasing data suggest that glutamate might act as a cell‐signaling molecule in non‐neuronal tissues such as the skin. Here we demonstrate the presence of functional N‐methyl‐d‐aspartate (NMDA)‐type glutamate receptors in human keratinocytes. NMDA receptor expression strongly reflects the degree of cell‐to‐cell contact. Wounding polarizes the expression of NMDA receptors in keratinocytes involved in re‐epithelialization, and the process of re‐epithelialization is inhibited by NMDA receptor activation. We also demonstrate that squamous cell carcinomas lack NMDA receptors. Our data suggest that Ca2+ entry through NMDA receptors influences the cycle of keratinocyte proliferation, differentiation, and migration during epithelialization. Moreover, NMDA receptor activation might play a role in contact‐mediated inhibition of growth, a process that is absent during neoplastic pathology. This receptor may serve as a pharmacological target for modulating keratinocyte behavior and treating cutaneous disorders.

Long-term bone marrow culture and its clinical potential in chronic wound healing

Bone marrow‐derived cells have long been regarded to play a crucial role in the homeostasis of skin. We have previously described the clinical benefit of directly applying autologous bone marrow aspirate and cultured bone marrow cells to recalcitrant chronic skin wounds. The initial response to treatment appears to be vascular in nature with the formation of new blood vessels. The difficulty in consistently growing adequate numbers of cells for delivery to patients was, however, a limiting factor. Here, in a subsequent protocol, we describe an improved bone marrow culture system yielding a reliable growth of bone marrow cells and leading to a greater clinical response. Cells expressing markers of endothelial progenitors including CD133, CD146, and particularly CD14 are enhanced in these cultures. CD14‐isolated cells produced colonies in endothelial cell assays and sprouting in matrigel assays. Angiogenic cytokines, including angiogenin, epithelial neutrophil‐activating protein‐78, growth‐regulated oncogene, growth‐regulated oncogene‐α, Interleukin‐8, CXC16, and monocyte chemoattractant protein‐1, were found to be elevated in these cultures. Administration of improved culture cells to patients with chronic wounds present for >1 year lead to an enhanced clinical response.

Resolution of Kaposi’s sarcoma associated with undetectable level of human herpesvirus 8 DNA in a patient with AIDS after protease inhibitor therapy ☆ ☆☆ ★ ★★

radiation. Acta Derm Venereol (Stockh) 1969;49:171-5. 3. Faessler R, Krebs A. Spatresultate von bestrahlten Plantarwarzen. Dermatologica 1974;148:345-52. 4. Schindl L, Kainz A, Kern H. Effect of low power laser irradiation on indolent ulcers caused by Buergers disease. Laser Ther 1992;4:25-31. 5. Karu T. Effects of visible radiation on cultured cells, yearly review. Photochem Photobiol 1990;52:1089-98. 6. Ghali L, Dyson M. The direct effect of light therapy on endothelial cell proliferation in vitro. In: Steiner R, Weisz PB, Langer R, editors. Angiogenesis key principles science technology medicine. Basel: Birkh~iuser Verlag; 1992. p. 411-4. 7. Steinlechner CWB, Dyson M. The effects of low level laser therapy on the proliferation of keratinocytes. Laser Ther 1993;5:65-73. 8. Baxter D. Therapeutic lasers: theory and practice. Edinburgh: Churchill Livingstone; 1994.

Hot pop brown spot: erythema Ab igne induced by heated popcorn.

Erythema ab igne is caused by chronic heat exposure and presents with reticulated pigmentation. Although various causes of erythema ab igne have been reported, in the United States, its incidence has been declining due to the advent of central heating. When seen, it is usually in the setting of local applications of a heated source, such as a hot water bottle, to treat muscular or arthritic pains. We report a novel cause of erythema ab igne occurring in a patient with chronic arthritic pains. This patient applied popcorn kernels, heated in a microwave, to his right wrist and knee for 30 minutes at a time for over four months.

Growth inhibition of primary keratinocytes following transduction with a novel TGFβ-1 containing retrovirus

Growth and migration of keratinocytes are known to be affected by the addition of exogenous cytokines, such as TGFbeta-1, to culture media. We have developed a retroviral vector, LNTbeta-1, that confers constitutive expression of human TGFbeta-1 to transduced cells. Keratinocytes were exposed to retroviral particles generated in serum-free media, and infected cells were selected for with Geneticin. Transduced keratinocytes remained in culture as single cells instead of a normally grouped growth pattern. While these transduced keratinocytes survived in culture for several weeks, they did not proliferate and seemed arrested in their growth. Keratinocytes transduced with retrovirus not containing the TGFbeta-1 gene appeared normal in their growth pattern. These findings indicate that high-level endogenous expression of TGFbeta-1 in keratinocytes can at least inhibit, and possibly arrest, growth.

Systemic 5-fluorouracil producing an inflammatory response in porokeratosis.

Topical 5‐fluorouracil has been used as an effective treatment for porokeratosis. Upon its treatment, an inflammatory effect occurs with the topical 5‐fluorouracil. We report a case of a patient with disseminated superficial actinic porokeratosis displaying a comparable inflammatory process following therapy with systemic 5‐fluorouracil used to manage a metastatic breast cancer.

Calciphylaxis with Peau D'Orange Induration and Absence of Classical Features of Purpura, Livedo Reticularis and Ulcers

Calciphylaxis is an ill‐defined syndrome that is commonly associated with chronic renal failure. Its heterogeneous clinical features include painful livedo reticularis‐like purpuric patches and plaques, vesicles, irregularly shaped ulcers, and black eschars. Despite demonstration of extensive vascular arteriolar calcification in this syndrome, its exact pathogenesis remains unknown. Here, we report a case of calciphylaxis presenting with indurated plaques without the usual clinical picture of livedo reticulate purpura, ulcers or necrotic eschars. This case provides an opportunity to review the clinical spectrum of calciphylaxis and to discuss the therapeutic approaches and pathogenesis of this syndrome from deep intra‐wall vascular calcification to the resulting infarctions of adjacent tissues.