Biomedical Sciences

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https://hdl.handle.net/10323/11884

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Browsing Biomedical Sciences by Subject "Biology"

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    Preclinical Studies: Treatment of Multiple Sclerosis and Retinal Degenerative Disease Using Stem Cells
    (2021-11-15) Cormier, Christina Frances; Chaudhry, G.; Govind, Chhabi; Svinarich, David; Perez-Cruet, Mick
    Pluripotent stem cells (PSCs) isolated from an embryo or generated by ectopic expression of transcription factors can self-renew indefinitely and differentiate into all cell types found in the body. PSCs have the highest potential for cell therapies, but they face ethical concerns and technical and safety challenges, including teratoma formation. In contrast, mesenchymal stem cells (MSCs) isolated from adult and perinatal sources do not pose ethical and moral dilemmas. While MSCs isolated from adult sources, such as bone marrow, require invasive procedures, their use may also cause graft verse host disease. Therefore, we have focused on MSCs isolated from perinatal sources such as the umbilical cord (UC). These cells have advantages over adult MSCs in that they are highly proliferative, do not display HLA-DR markers, and thus are not likely to be immunogenic. We tested the therapeutic efficacy of UC-derived MSCs and their derivatives in preclinical studies to treat multiple sclerosis (MS) and retinal degenerative disease (RDD). The specific aims were to 1. production of MSCs for preclinical studies; 2. treatment of MS using MSCs and NSCs; and 3. treatment of RDD using MSCs and RPC. Our results showed that MSC-derived neural stem cells (NSCs) countered the inflammatory response, provided neural protection, and induced neurogenesis in the experimental autoimmune encephalomyelitis (EAE) mouse model of MS. Likewise, MSC-derived retinal progenitor cells (RPCs) survived, integrated, and migrated into various neural layers of the retina in the rd12 mouse model of retinitis pigmentosa (RP). RPCs promoted retinal structure, function, neural protection, and regeneration of the retina resulting in vision improvement. These highly promising findings are likely to facilitate clinical studies for treating MS and RDD.
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    The Role of CD49f - Integrin α6- in Human Stem Cell Biology
    (2021-11-15) Timilsina, Suraj; Villa-Diaz, Luis; K. Lal, Shailesh; Madlambayan, Gerard
    Owing to the intrinsic capability for unlimited self-renewal and the ability to make all the cells in the body, pluripotent stem cells (PSC) are an ideal candidate to be used as starting material for cell therapies. The development of a standard human PSC (hPSC), which includes embryonic stem cells (hESC) and induced pluripotent stem cells (hiPSC), culture methods using completely defined and xeno-free culture environment will advance our knowledge of hPSC biology, and also increase the effectiveness of hPSC expansion on defined conditions for potential human applications. It has been shown that stem cell fates are controlled by their specialized microenvironment, the stem cell niche, via direct cell-cell interactions, cell-extracellular matrix (ECM) contact- largely by surface proteins known as integrins- and the molecular signals emitting from the niche. Activation of integrins by binding to their ligands triggers signal transduction mechanisms involved in cell fate determination. In addition, because of their cell surface localization, integrins are used as biological markers to identify cell populations, and in this regard, integrin α6 (ITGA6), also known as CD49f, is a key biomarker identifying stem cells as it is commonly expressed in all identified stem cell types. Although, numerous findings strongly suggest that CD49f plays important functions in stem cell biology, the underlying molecular mechanisms by which CD49f sustain stem cell’s self-renewal have been only partially described. In this project I have established a chemically defined and xeno-free culture condition for long-term maintenance and derivation of hPSC using chemically defined and xeno-free culture conditions. I also described a novel molecular mechanism involved in the maintenance of self-renewal and proliferation of hPSC using simulated microgravity (sμg). Moreover, my results highlighted CD49f as a reliable biomarker in identifying and characterizing functional status of human mesenchymal stem cells (hMSC).