Dermal hematopoietic stem cells

The prodigious ability of the embryo to differentiate and of certain adult tissues to regenerate throughout life directly derives from the properties of stem cells. Stem cells have the capacity to self-renew, i.e. divide to form identical daughter stem cells, as well as the ability to generate differentiated cells. Recent evidence suggests that stem cells are not only present in the embryo but in fact in each adult tissue. The epidermis is an excellent example of an adult tissue which depends on tissue-resident stem cells for its maintenance and regeneration. It is therefore tempting to speculate that dermal stem cells may play the equivalent role in replacing dermal cells in dermal repair, may be involved in regulating the cellularity of normal dermis, and moreover, of hematopoietic cells in the dermis (dermal dendritic cells) and epidermis (e.g. Langerhans cells). Indeed evidence exists that the dermis contains cells which have the capacity to differentiate into multiple cell types, suggesting that there may be a multipotent stem cell, the phenotype of which is still unclear. We want to elucidate whether the murine and human dermis contains hematopoietic stem cells (HSC) and if so (i) to identify them with selected markers, (ii) to examine their gene and cytokine expression pattern, (iii) to test their in vitro clonogenic capacity, (iv) to assess their in vivo repopulation potential, and (v) to define their origin. Easy accessibility of skin will make dermal HSC an ideal vehicle for genetic manipulation and gene therapy for the treatment of skin disorders and systemic deficiences. The ability to identify, isolate and grow these cells represents an important prerequisite for the development of these approaches and will furthermore, provide a basis to study the biological role for endogenous CD45 + and/or CD45 - dermal stem cells in maintaining skin tissue integrity by participating in regeneration.

The prodigious ability of the embryo to differentiate and of certain adult tissues to regenerate throughout life directly derives from the properties of stem cells. Stem cells have the capacity to self-renew, i.e. divide to form identical daughter stem cells, as well as the ability to generate differentiated cells. Recent evidence suggests that stem cells are not only present in the embryo but in fact in each adult tissue. The epidermis is an excellent example of an adult tissue which depends on tissue-resident stem cells for its maintenance and regeneration. It is therefore tempting to speculate that dermal stem cells may play the equivalent role in replacing dermal cells in dermal repair, may be involved in regulating the cellularity of normal dermis, and moreover, of hematopoietic cells in the dermis (dermal dendritic cells) and epidermis (e.g. Langerhans cells). Indeed evidence exists that the dermis contains cells which have the capacity to differentiate into multiple cell types, suggesting that there may be a multipotent stem cell, the phenotype of which is still unclear. We want to elucidate whether the murine and human dermis contains hematopoietic stem cells (HSC) and if so (i) to identify them with selected markers, (ii) to examine their gene and cytokine expression pattern, (iii) to test their in vitro clonogenic capacity, (iv) to assess their in vivo repopulation potential, and (v) to define their origin. Easy accessibility of skin will make dermal HSC an ideal vehicle for genetic manipulation and gene therapy for the treatment of skin disorders and systemic deficiences. The ability to identify, isolate and grow these cells represents an important prerequisite for the development of these approaches and will furthermore, provide a basis to study the biological role for endogenous CD45 + and/or CD45 - dermal stem cells in maintaining skin tissue integrity by participating in regeneration.