Induced Pluripotent Stem Cell Therapies for Degenerative Disease of the Outer Retina: Disease Modeling and Cell Replacement

Foggia, Valentina Di; Makwana, Priyanka; Ali, Robin R.; Sowden, Jane C.

doi:10.1089/jop.2015.0143

Cited by 14 publications

(10 citation statements)

References 134 publications

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“…Given the overall modest outcomes to date, cultured Müller glia seem unlikely to provide a clinically relevant path for generating sufficiently large numbers of retinal progenitors for transplantation. Successful regenerative strategies using transplantation are more likely to build on the ongoing progress in generating retinal progenitors and neurons from other sources, such as induced pluripotent stem cells [ 3 – 6 , 15 , 177 – 184 ]. Therefore, the importance of studies to promote in vitro differentiation of Müller glia lies in the ability to manipulate the cellular environment and to dissect cellular mechanisms that regulate their regenerative responses.…”

Section: Discussionmentioning

confidence: 99%

Regulation of Stem Cell Properties of Müller Glia by JAK/STAT and MAPK Signaling in the Mammalian Retina

Beach

Wang

Otteson

2017

Stem Cells International

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In humans and other mammals, the neural retina does not spontaneously regenerate, and damage to the retina that kills retinal neurons results in permanent blindness. In contrast to embryonic stem cells, induced pluripotent stem cells, and embryonic/fetal retinal stem cells, Müller glia offer an intrinsic cellular source for regenerative strategies in the retina. Müller glia are radial glial cells within the retina that maintain retinal homeostasis, buffer ion flux associated with phototransduction, and form the blood/retinal barrier within the retina proper. In injured or degenerating retinas, Müller glia contribute to gliotic responses and scar formation but also show regenerative capabilities that vary across species. In the mammalian retina, regenerative responses achieved to date remain insufficient for potential clinical applications. Activation of JAK/STAT and MAPK signaling by CNTF, EGF, and FGFs can promote proliferation and modulate the glial/neurogenic switch. However, to achieve clinical relevance, additional intrinsic and extrinsic factors that restrict or promote regenerative responses of Müller glia in the mammalian retina must be identified. This review focuses on Müller glia and Müller glial-derived stem cells in the retina and phylogenetic differences among model vertebrate species and highlights some of the current progress towards understanding the cellular mechanisms regulating their regenerative response.

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Section: Discussionmentioning

confidence: 99%

Regulation of Stem Cell Properties of Müller Glia by JAK/STAT and MAPK Signaling in the Mammalian Retina

Beach

Wang

Otteson

2017

Stem Cells International

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“…The only stem cell treatment which fulfills the criteria of clinical routine is hematopoietic stem cell transplantation. All the “therapies” using nonhematopoietic stem cells (induced pluripotent stem cells [ 16 ], embryo cells [ 17 ], fetal stem cells [ 18 ], or adult stem cells [ 19 ]) are still at the experimental stage. The beginnings of stem cell applications for regenerative medicine purpose, dated at the beginning of 21st century, were based on the expectation of tissue reconstruction by transplanted cells themselves.…”

Section: Resultsmentioning

confidence: 99%

Adipose‐Derived Cells (Stromal Vascular Fraction) Transplanted for Orthopedical or Neurological Purposes: Are They Safe Enough?

Siennicka

Zołocińska

Stępień³

et al. 2016

Stem Cells International

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Although mesenchymal stem cells are used in numerous clinical trials, the safety of their application is still a matter of concern. We have analysed the clinical results of the autologous adipose-derived stem cell treatment (stromal vascular fraction (SVF) containing adipose-derived stem cells, endothelial progenitors, and blood mononuclear cells) for orthopedic (cartilage, bone, tendon, or combined joint injuries) and neurologic (multiple sclerosis) diseases. Methods of adipose tissue collection, cell isolation and purification, and resulting cell numbers, viability, and morphology were considered, and patient's age, sex, disease type, and method of cell administration (cell numbers per single application, treatment numbers and frequency, and methods of cell implantation) were analysed and searched for the unwanted clinical effects. Results of cellular therapy were compared retrospectively to those obtained with conventional medication without SVF application. SVF transplantation was always the accessory treatment of patients receiving “standard routine” therapies of their diseases. Clinical experiments were approved by the Bioethical Medical Committees supervising the centers where patients were hospitalised. The conclusion of the study is that none of the treated patients developed any serious adverse event, and autologous mesenchymal stem (stromal) cell clinical application is a safe procedure resulting in some beneficial clinical effects (not analysed in this study).

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“…In 2006, the Japanese scholar Shinya Yamanaka published on the induced pluripotent stem cell (iPSC) technology for the first time [ 20 ]. In recent years, this technology has attracted the attention of many scholars and business groups because of its promising applications in the field of regenerative medicine [ 21 – 24 ]. Although iPSC technology still has some problems, such as low induction rates, incomplete reprogramming, and potential biological safety issues arising from the necessary use of viral vectors [ 25 ], sooner or later these problems will be overcome through technological development.…”

Section: Discussionmentioning

confidence: 99%

Cell therapy could be a potential way to improve lipoprotein lipase deficiency

Yin

Zhong

et al. 2017

Lipids Health Dis

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BackgroundLipoprotein lipase (LPL) deficiency is an autosomal recessive genetic disorder characterized by extreme hypertriglyceridemia, with no cure presently available. The purpose of this study was to test the possibility of using cell therapy to alleviate LPL deficiency.MethodsThe LPL coding sequence was cloned into the MSCV retrovirus vector, after which MSCV-hLPL and MSCV (empty construct without LPL coding sequence) virion suspensions were made using the calcium chloride method. A muscle cell line (C2C12), kidney cell line (HEK293T) and pre-adipocyte cell line (3 T3-L1) were transfected with the virus in order to express recombinant LPL in vitro. Finally, each transfected cell line was injected subcutaneously into nude mice to identify the cell type which could secret recombinant LPL in vivo. Control cells were transfected with the MSCV empty vector. LPL activity was analyzed using a radioimmunoassay.ResultsAfter virus infection, the LPL activity at the cell surface of each cell type was significantly higher than in the control cells, which indicates that all three cell types can be used to generate functional LPL. The transfected cells were injected subcutaneously into nude mice, and the LPL activity of the nearby muscle tissue at the injection site in mice injected with 3 T3-L1 cells was more than 5 times higher at the injection sites than at non-injected control sites. The other two types of cells did not show this trend.ConclusionThe subcutaneous injection of adipocytes overexpressing LPL can improve the LPL activity of the adjacent tissue of nude mice. This is a ground-breaking preliminary study for the treatment of LPL deficiency, and lays a good foundation for using cell therapy to correct LPL deficiency.

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Induced Pluripotent Stem Cell Therapies for Degenerative Disease of the Outer Retina: Disease Modeling and Cell Replacement

Cited by 14 publications

References 134 publications

Regulation of Stem Cell Properties of Müller Glia by JAK/STAT and MAPK Signaling in the Mammalian Retina

Regulation of Stem Cell Properties of Müller Glia by JAK/STAT and MAPK Signaling in the Mammalian Retina

Adipose‐Derived Cells (Stromal Vascular Fraction) Transplanted for Orthopedical or Neurological Purposes: Are They Safe Enough?

Cell therapy could be a potential way to improve lipoprotein lipase deficiency

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