Katarina Jansson

The Adult Human Brain Harbors Multipotent Perivascular Mesenchymal Stem Cells

Blood vessels and adjacent cells form perivascular stem cell niches in adult tissues. In this perivascular niche, a stem cell with mesenchymal characteristics was recently identified in some adult somatic tissues. These cells are pericytes that line the microvasculature, express mesenchymal markers and differentiate into mesodermal lineages but might even have the capacity to generate tissue-specific cell types. Here, we isolated, purified and characterized a previously unrecognized progenitor population from two different regions in the adult human brain, the ventricular wall and the neocortex. We show that these cells co-express markers for mesenchymal stem cells and pericytes in vivo and in vitro, but do not express glial, neuronal progenitor, hematopoietic, endothelial or microglial markers in their native state. Furthermore, we demonstrate at a clonal level that these progenitors have true multilineage potential towards both, the mesodermal and neuroectodermal phenotype. They can be epigenetically induced in vitro into adipocytes, chondroblasts and osteoblasts but also into glial cells and immature neurons. This progenitor population exhibits long-term proliferation, karyotype stability and retention of phenotype and multipotency following extensive propagation. Thus, we provide evidence that the vascular niche in the adult human brain harbors a novel progenitor with multilineage capacity that appears to represent mesenchymal stem cells and is different from any previously described human neural stem cell. Future studies will elucidate whether these cells may play a role for disease or may represent a reservoir that can be exploited in efforts to repair the diseased human brain.

Characterization of a newin vitro model for studies of reepithelialization in human partial thickness wounds

SummaryReepithelialization of artificial partial thickness wounds made in biopsies of human skin was determined after 3, 5, or 7 d of incubation, submerged or elevated to the air-liquid interface. The biopsies were reepithelialized within 5–7 d, with a more complete epidermal healing in wounds exposed to air. Both types of wounds showed similar time-course in deposition of basement membrane components, as detected by immunofluorescence labeling. Laminin and collagen type VII were deposited underneath the migrating tips, whereas collagen type IV was detected after reepithelialization. Markers of terminal differentiation showed a pattern close to normal in the air-liquid incubated wounds after reepithelialization. Involucrin was detected in the suprabasal regions of the migrating epidermis and thereafter in the upper half of neo-epidermis in the air-liquid incubated wound. Filaggrin could not be detected in the submerged wounds at any time during healing, whereas wounds exposed to air showed a well-differentiated epidermis by Day 7. Tritiated thymidine-incorporation indicated proliferation of epidermal and dermal cells during reepithelialization and a maintained viability, as shown by cultivation of endothelial- and fibroblast-like cells obtained from the dermis 7 d after wounding.Reepithelialization in this humanin vitro model is supported by a matrix close to normal with the possibility of extracellular influences and cell-cell interactions and, in addition, the technique is simple and reproducible. Therefore, we suggest this model for studies of regeneration in culture and as a complement toin vivo studies on epidermal healing.

A biodegradable bovine collagen membrane as a dermal template for human in vivo wound healing.

A bovine collagen membrane was used as a template for dermal regeneration in human full thickness wounds. Healing was allowed for 7, 21, or 42 days. The formation of neodermis, basement membrane, and terminal differentiation were assessed histologically and immunohistochemically. The collagen template was neovascularised within 7 days, and from day 21 small vessels were detected throughout the transplanted area. The procollagen content decreased whereas the number of fibroblasts increased with time. Collagen type IV was not detected after 7 days but was deposited with time from the wound edges and inwards over the transplanted area. Re-epithelialisation was complete at day 7 and terminal differentiation was similar to normal human skin from day 21. We have shown the time course of dermal and epidermal healing with the aid of a ready-to-use biodegradable collagen membrane. This material may be used as a true dermal template because of the evidence of dermal regeneration and, in addition, its availability and ease of handling.A bovine collagen membrane was used as a template for dermal regeneration in human full thickness wounds. Healing was allowed for 7, 21, or 42 days. The formation of neodermis, basement membrane, and terminal differentiation were assessed histologically and immunohistochemically. The collagen template was neovascularised within 7 days, and from day 21 small vessels were detected throughout the transplanted area. The procollagen content decreased whereas the number of fibroblasts increased with time. Collagen type IV was not detected after 7 days but was deposited with time from the wound edges and inwards over the transplanted area. Re-epithelialisation was complete at day 7 and terminal differentiation was similar to normal human skin from day 21. We have shown the time course of dermal and epidermal healing with the aid of a ready-to-use biodegradable collagen membrane. This material may be used as a true dermal template-because of the evidence of dermal regeneration and, in addition, its availability and ease of handling.