Multipotent stem cells differentiation

Figure 2.1. Development of blood cells. The development of blood cells occurs in the bone marrow. All cells arise from the differentiation of pluripotent or multipotent stem cells, which have the capacity for self-renewal, or else can divide into more mature cells types. The morphological features of the mature blood cell types is shown.

It is believed that all blood cells arise from the division and differentiation of multipotent stem cells. These stem cells have considerable capacity for self-renewal by cell division but may also differentiate into progenitor cells of lymphocytic or myeloid lineages (see Fig. 2.1). Experiments with colony-... 

The therapeutic application of stem cells has long been a dream of medical sciences, but recent discoveries and technical advances have brought this dream much closer to being a reality. Stem cells are usually defined as undifferentiated cells capable of self-renewal, which can differentiate into more than one specialized cell type. Pluripotent stem cells are capable of essentially differentiating into any cell type, whereas multipotent stem cells, often found (be it in low numbers) within specific organs, give rise to lineage-restricted, tissue-specific cell types (see also Part I, Chapter 13). Human embryonic stem cells, harvested from the inner mass... 

Even though these populations are localized in adult tissues having lineage-commitment and exhibiting limited plasticity and local cell markers, some of these cells are capable of de-differentiating and then becoming multipotent stem cells. 

Pluripotent/multipotent stem cells with relative ease in isolation have become an attractive choice for cell encapsulation where differentiated products are required. Table 8.1 shows encapsulated stan cells undergoing differentiation along defined lineages. In addition to replacing damaged cells, stem cells also secrete various trophic factors that help to improve tissue function and regeneration. 

Although gastric multipotent stem cells have not been isolated, the genetic analysis of an enriched mouse gastric epithelial progenitor cell population from the fundus has facilitated the understanding of some of the molecular pathways that regulate this precursor cell proliferation and differentiation in the murine stomach. 

The mechanical capacity of polymers is often enhanced by the formation of composite structures composed of (1) oriented reinforcing imits, such as fibrils, fibers, or extended chain crystals and (2) the use of binding matrices of the same chemical structure [133]. An alternative that mediates improved mechanical performance while providing space for cellular invasion is the deposition of a bonelike mineral film on the interior pore surfaces of PLGA scaffolds (Fig. 8) [ 134,135]. This approach not only leads to increased compressive moduli, but also confers the scaffolds with osteoconductive characteristics and the ability to modulate proliferation and differentiation of multipotent stem cells [134-137]. 

The bone marrow is a rich source of multipotent stem cells. For cardiac repair, many investigators use unfractionated bone marrow cells (BMC) which include hematopoietic stem cells (HSC), endothelial progenitor cells (EPC), and mesenchymal stem cells (MSC). This strategy provides ease in cell accessibility and does not require extensive manipulation in vitro. HSC are located in the bone marrow and are multipotent stem cells that give rise to several types of cells including red blood cells, white blood cells, and platelets. Interestingly, it has been noted that HSC transplanted into murine myocardium may differentiate into cardiomyocytes and blood vessels (Orlic et al., 2003). EPC can be mobilized using cytokines and can be isolated from peripheral blood or bone marrow. Several reports have demonstrated the ability of EPC to revascularize myocardium after an Ml (Kocher et al., 2001). 

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