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Publisher: Springer international Publishing AgSubject: Hematopoietic stem cell

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    Citation - WoS: 3
    Citation - Scopus: 4
    Stem Cell Applications in Lysosomal Storage Disorders: Progress and Ongoing Challenges
    (Springer international Publishing Ag, 2021) Kose, S.; Aerts-Kaya, F.; Cetinkaya, D. Uckan; Korkusuz, P.
    Lysosomal storage disorders (LSDs) are rare inborn errors of metabolism caused by defects in lysosomal function. These diseases are characterized by accumulation of completely or partially degraded substrates in the lysosomes leading to cellular dysfunction of the affected cells. Currently, enzyme replacement therapies (ERTs), treatments directed at substrate reduction (SRT), and hematopoietic stem cell (HSC) transplantation are the only treatment options for LSDs, and the effects of these treatments depend strongly on the type of LSD and the time of initiation of treatment. However, some of the LSDs still lack a durable and curative treatment. Therefore, a variety of novel treatments for LSD patients has been developed in the past few years. However, despite significant progress, the efficacy of some of these treatments remains limited because these therapies are often initiated after irreversible organ damage has occurred. Here, we provide an overview of the known effects of LSDs on stem cell function, as well as a synopsis of available stem cell-based cell and gene therapies that have been/are being developed for the treatment of LSDs. We discuss the advantages and disadvantages of use of hematopoietic stem cell (HSC), mesenchymal stem cell (MSC), and induced pluripotent stem cell (iPSC)-related (gene) therapies. An overview of current research data indicates that when stem cell and/or gene therapy applications are used in combination with existing therapies such as ERT, SRT, and chaperone therapies, promising results can be achieved, showing that these treatments may result in alleviation of existing symptoms and/or prevention of progression of the disease. All together, these studies offer some insight in LSD stem cell biology and provide a hopeful perspective for the use of stem cells. Further development and improvement of these stem cell (gene) combination therapies may greatly improve the current treatment options and outcomes of patients with a LSD.
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    Citation - WoS: 15
    Citation - Scopus: 15
    Comparison of Hematopoietic and Spermatogonial Stem Cell Niches From the Regenerative Medicine Aspect
    (Springer international Publishing Ag, 2018) Kose, Sevil; Yersal, Nilgun; Onen, Selin; Korkusuz, Petek
    Recent advances require a dual evaluation of germ and somatic stem cell niches with a regenerative medicine perspective. For a better point of view of the niche concept, it is needed to compare the microenvironments of those niches in respect to several components. The cellular environment of spermatogonial stem cells' niche consists of Sertoli cells, Leydig cells, vascular endothelial cells, epididymal fat cells, peritubular myoid cells while hematopoietic stem cells have mesenchymal stem cells, osteoblasts, osteoclasts, megacaryocytes, macrophages, vascular endothelial cells, pericytes and adipocytes in their microenvironment. Not only those cells', but also the effect of the other factors such as hormones, growth factors, chemokines, cytokines, extracellular matrix components, biomechanical forces (like shear stress, tension or compression) and physical environmental elements such as temperature, oxygen level and pH will be clarified during the chapter. Because it is known that the microenvironment has an important role in the stem cell homeostasis and disease conditions, it is crucial to understand the details of the microenvironment and to be able to compare the niche concepts of the different types of stem cells from each other, for the regenerative interventions. Indeed, the purpose of this chapter is to point out the usage of niche engineering within the further studies in the regenerative medicine field. Decellularized, synthetic or non-synthetic scaffolds may help to mimic the stem cell niche. However, the shared or different characteristics of germ and somatic stem cell microenvironments are necessary to constitute a proper niche model. When considered from this aspect, it is possible to produce some strategies on the personalized medicine by using those artificial models of stem cell microenvironment.