Download or read book Sourcing and Modulation of the Fate of Connective Tissue Progenitors written by Maha Ahmad Qadan and published by . This book was released on 2016 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Stem and progenitor cells are a key component of regenerative medicine with the potential to fully heal damaged tissues and organs, offering ultimate solutions for people who live with long-suffering conditions; such as diabetes, heart failure, and degenerative nerve, bone, and joint pathologies, that today are beyond repair. All tissue formation, regeneration or repair requires a population of cells (i.e. stem cells or progenitor cells) that can be activated to proliferate and/or differentiate, generating progeny that will contribute to the formation of new tissue. Hierarchical populations of stem and progenitor cells have been defined, with varying degrees of precision, in many tissues. Understanding the kinetics of tissue remodeling and responses to disease is increasingly important for the development of therapies in settings where the stem/progenitor population has become deficient or dysfunctional. Understanding of these systems is also essential for the rational optimization of cell sourcing and processing strategies for cell therapy applications. Regeneration and repair of tissues depend on stem and progenitor cell populations that are resident in tissues. The choice of the source of cells for tissue engineering or cell therapy applications depends mainly on factors such as the ease of harvest, low morbidity, consistency (with respect to the yield and biological potential). Several cell populations from various tissues have been isolated and characterized. Bone marrow-derived mesenchymal stromal cells (BM-MSCs) have been considered as a source of multipotent cells and can be derived from various tissue sources. However, controversial findings, with respect to the best tissue source for isolation and utilization in regenerative applications, have been presented 9. Therefore, an alternative source of cell populations with better proliferation potential and defined marker profile represents a promising tool in clinical applications. Connective tissue progenitors (CTPs) represent a candidate cell source. These are heterogeneous stem and progenitor cell populations present in native tissue that are able to proliferate and differentiate in vitro into one or more connective tissue phenotypes. CTPs are essential to the formation and remodeling of connective tissue, and therefore a key target cell population and cell source for tissue engineering and cell-based therapies focused on tissue regeneration. CTPs are found in virtually every connective tissue (bone, cartilage, fat, blood). Several previous studies have described differences between tissue sources with respect to biological potential. Variation has been reported between patients, related to age, gender, surgical site, and harvesting techniques. The culture-expanded populations, derived from CTPs, demonstrate variations between tissues and among batches from the same tissue, as well as heterogeneity within an apparent clone. Adipose tissue and bone are the two most abundant sources of CTPs. However, the biological potential of these sources varies. The International Society for Cellular Therapy (ISCT) has defined standards based on a surface marker profile for classification of culture-expanded cells as mesenchymal stromal cells (MSCs). However, recent data demonstrate that expression of this MSC profile of markers is not predictive of biological behavior with respect to bone, cartilage and fat differentiation in vitro. Therefore, expressing typical MSC surface markers may not be sufficient to discriminate between critical attributes of biological potential. Other surface markers, which are more predictive of differences in biological potential need to be considered. A variety of other markers such as; pluripotency-associated markers, both transcription factors and surface markers, could serve as candidates for in depth investigation to reflect the biological potential of a given cell population. The response of CTPs in terms of proliferation, migration, differentiation and survival, depends on the number of progenitors present, the intrinsic state of the cells, their biological potential, and the microenvironment in the region of injury or disease. The response of progenitors within a given region of tissue and their fate may also be dependent on the presence or absence of other biological active cells that may secrete bioactive factors or matrix elements that impact on the microenvironment over time. CTPs from almost all sources are multipotent. This means that the progeny of a CTP may be modulated to express one or more of a variety of phenotypes in vitro or in vivo (e.g. bone, cartilage, fat or fibrous tissue). The fate of an individual CTP may be changed by the microenvironment created by the chemical composition (glucose, oxygen), soluble factors (growth factors, cytokines), other factors (microRNAs, microvesicles). Glucose concentration, as a clinically relevant factor, may determine the relative tendency of CTPs to choose an osteogenic fate (bone formation) versus an adipocytic fate (fat formation). Glucose concentration may have relevance to fracture repair as well as the maintenance of bone health (e.g. avoidance of osteoporosis). Diabetes has been associated with delayed fracture repair, accelerated age-related bone loss and increased risk of osteoporosis. The possible mechanisms of these changes have been extensively studied, but are not completely understood. Knowledge of the concentration and prevalence of CTPs in native tissues and variation in their biological properties and potential is an essential step in the rational selection of cell sources for tissue engineering applications, and the design of reproducible methods for fabrication of cell populations for cell therapies. Understanding the variation in the biological potential among CTPs with respect to sensitivity to glucose concentration and the effects of exposure to high glucose concentration on the fate of CTP progeny have important implications in understanding the potential interaction between glucose control in diabetes and the preservation of bone and bone marrow health as well as fracture healing potential.