Читать книгу The SAGE Encyclopedia of Stem Cell Research - Группа авторов - Страница 145

It is challenging to recreate the microenvironment of the stem cell niche for ex vivo multiplication of HSCs. Cultured HSCs lose their ability to engraft and divide in vivo, which severely limits the process of in vitro manipulation and growth for therapeutic purposes.

Nevertheless, it is a continuing endeavor to produce patient-specific stem cells, particularly HSCs in comparatively larger quantities in vitro. These are preferred for autologous stem cell therapy, and would circumvent the development of adverse clinical reactions and infections. A recent study reported successful dedifferentiation (reprogramming) of connective tissue cells such as fibroblasts into HSCs by using a combination of eight transcription factors. It indicates the generation of induced pluripotent cells (iPSCs) with the transduction of defined transcription factors. Interest has lately shifted to reprogramming of mononuclear cells from peripheral blood into iPSCs and their in vitro/in vivo conversion to mesenchymal stem cells, hepatocytes, or neural cells. This reprogramming has its challenges and is being achieved by genetic modification using lentiviral vectors, as well as the Sendai virus and other episomal factors.

Another experiment successfully demonstrated the plasticity of adult stem cells when purified HSCs restored the biochemical function of the liver in deficient mice. This phenomenon, also known as transdifferentiation, defines the pluripotent nature of blood stem cells. It is, however, not a regular phenomenon and the mechanisms behind it are not fully understood. HSCs, along with CD34 (adhesion factor), have also been used to treat spinal cord injury, liver cirrhosis, and peripheral vascular disease. Stem cells isolated from peripheral blood as well as UCB were observed to differentiate into endothelial-like cells, which could be incorporated into hypoxic tissues, as seen in ischemic cardiomyopathies. They promoted neovascularization and tissue repair following an enhanced oxygen and nutrient supply. This plasticity of stem cells can be exploited to plan therapeutic interventions in regenerative medicine.

Since they can generate parenchymatous cells, such as myocytes, hepatocytes, endothelial and myocardial cells, and neuronal and glial cells, HSCs can be used to repair damaged tissues in the body. Besides this, they secrete growth factors, chemokines, and cytokines, which encourage angiogenesis as well as suppress inflammation and cell death. It is expected that age-related functional defects; hematopoietic and immune system disorders; heart failures; chronic liver injuries; diabetes; neurodegenerative disorders such as Parkinson’s and Alzheimer’s diseases; arthritis; and muscular, skin, lung, eye, and digestive disorders, as well as aggressive and recurrent cancers, could be successfully treated by stem cell-based therapies. A pediatric population comprising adolescents, infants, and children with Down syndrome have also undergone HSC transplantation for leukemia, and the results are being evaluated for improvement of the outcome. They do show higher treatment-related toxicity and mortality.

A review of the ongoing clinical trials, as well as a literature search, revealed that UCB-based therapies are being increasingly used in nonhematopoietic diseases, particularly neurologic disorders. Cellular regeneration and immune modulation are the other targets of UCB transplantation.