Browsing by Author "Perez-Cruet, Mick"

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    Isolation and comparative analysis of potential stem/progenitor cells from different regions of human umbilical cord
    (2016-10-27) Beeravolu, Naimisha; Khan, Irfan; McKee, Christina; Dinda, Sumi; Thibodeau, Bryan; Wilson, George; Perez-Cruet, Mick; Bahado-Singh, Ray; Chaudhry, G. Rasul
    Human umbilical cord (hUC) blood and tissue are non-invasive sources of potential stem/progenitor cells with similar cell surface properties as bone marrow stromal cells (BMSCs). While they are limited in cord blood, they may be more abundant in hUC. However, the hUC is an anatomically complex organ and the potential of cells in various sites of the hUC has not been fully explored.We dissected the hUC into its discrete sites and isolated hUC cells from the cord placenta junction (CPJ), cord tissue (CT), and Wharton's jelly (WJ). Isolated cells displayed fibroblastoid morphology, and expressed CD29, CD44, CD73, CD90, and CD105, and showed evidence of differentiation into multiple lineages in vitro. They also expressed low levels of pluripotency genes, OCT4, NANOG, SOX2 and KLF4. Passaging markedly affected cell proliferation with concomitant decreases in the expression of pluripotency and other markers, and an increase in chondrogenic markers. Microarray analysis further revealed the differences in the gene expression of CPJ-, CT- and WJ-hUC cells. Five coding and five lncRNA genes were differentially expressed in low vs. high passage hUC cells. Only MAEL was expressed at high levels in both low and high passage CPJ-hUC cells. They displayed a greater proliferation limit and a higher degree of multi-lineage differentiation in vitro and warrant further investigation to determine their full differentiation capacity, and therapeutic and regenerative medicine potential.
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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.