Generating and replacing
Differentiated and mature cells in tissues
Stem cells (SCs), common to all multicellular organisms, are defined as undifferentiated self-replicating cells that can generate, sustain and replace differentiated and mature cells in the tissues. Two important features of SCs are: self-renewal (cell divisions with maintenance of the undifferentiated state), and capability of self-organization to specific tissues via differentiation into specialized cell types. SCs are commonly subdivided into two main entities, embryonic stem cells (ESCs) (pluripotent) and adult SCs (multipotent or unipotent).
Recently, “embryonic-like” cells, so-called induced pluripotent cells (iPSCs), have been added in the last years. iPSCs are developed through genetic manipulation of differentiated (somatic) cells. Reprogramming of somatic cells to iPSCs provides an important (infinitely expandable ex vivo) cell source to develop customized, patient-specific cells with diverse and specialized cellular phenotypes for potential therapeutic applications. Skin cells, e.g. dermal fibroblasts, keratinocytes, dermal papilla cells or melanocytes, are preferentially used for this technique due to easy accessibility in the patient via isolation from punch biopsies.
Multipotent Mesenchymal Stromal Cells (MSCs)
Mesenchymal (stem) stromal cells (MSCs) were first identified as fibroblast precursors in bone marrow in the 1950s. Since then, MSCs have been obtained from several tissues, including adipose tissue (fat), skin, umbilical cord blood, placenta, peripheral blood, endometrium, dental pulp, dermis and amniotic fluid. The trophic, paracrine and immunomodulatory functions of these cells, besides the differentiation-capability in vitro, may have the biggest therapeutic implication in vivo.
One of the main functions of MSCs is to support repair of damaged tissues by migrating towards injury sites, differentiate and operate through the release of molecules participating in tissue regeneration.
Up to date more than 600 clinical trials are listed in the U. S. National Institutes of Health database (www.clinicaltrials. gov) dealing with MSC therapy for various diseases such as different forms of cancer, spinal cord injury, multiple sclerosis, Parkinson's disease, myocardial infarction, rheumatoid arthritis and graft-versus-host-disease (GVHD). However, current research strategies try to increase the efficiency of therapeutically administered MSCs by mainly encountering their limited persistence in vivo.