Adult Stem Cell Therapeutics in Diabetic Retinopathy
Abstract
:1. Diabetes and Diabetic Retinopathy
2. Adult Stem Cells
3. Stem Cell Alterations
4. Paracrine Nature of Stem Cells
5. Clinical Trials
6. Limitations of Stem Cell Therapies and Future Directions
Author Contributions
Funding
Conflicts of Interest
References
- CDC. Diabetes. Available online: https://www.cdc.gov/media/presskits/aahd/diabetes.pdf (accessed on 6 July 2019).
- CDC. New CDC Report: More than 100 Million Amercans Have Diabetes or Prediabetes; CDC: Atlanta, GA, USA, 2017.
- NIH. Facts About DIabetic. 2015. Available online: https://nei.nih.gov/health/diabetic/retinopathy (accessed on 7 July 2019).
- Wong, T.Y.; Cheung, C.M.; Larsen, M.; Sharma, S.; Simo, R. Diabetic retinopathy. Nat. Rev. Dis. Primers 2016, 2, 16012. [Google Scholar] [CrossRef] [PubMed]
- Fiori, A.; Terlizzi, V.; Kremer, H.; Gebauer, J.; Hammes, H.P.; Harmsen, M.C.; Bieback, K. Mesenchymal stromal/stem cells as potential therapy in diabetic retinopathy. Immunobiology 2018, 223, 729–743. [Google Scholar] [CrossRef] [PubMed]
- Hernandez, C.; Simo-Servat, A.; Bogdanov, P.; Simo, R. Diabetic retinopathy: New therapeutic perspectives based on pathogenic mechanisms. J. Endocrinol. Investig. 2017, 40, 925–935. [Google Scholar] [CrossRef] [PubMed]
- Heng, L.Z.; Comyn, O.; Peto, T.; Tadros, C.; Ng, E.; Sivaprasad, S.; Hykin, P.G. Diabetic retinopathy: Pathogenesis, clinical grading, management and future developments. Diabet. Med. 2013, 30, 640–650. [Google Scholar] [CrossRef] [PubMed]
- Falavarjani, K.G.; Nguyen, Q.D. Adverse events and complications associated with intravitreal injection of anti-VEGF agents: A review of literature. Eye 2013, 27, 787–794. [Google Scholar] [CrossRef] [PubMed]
- Emre, E.; Yuksel, N.; Duruksu, G.; Pirhan, D.; Subasi, C.; Erman, G.; Karaoz, E. Neuroprotective effects of intravitreally transplanted adipose tissue and bone marrow-derived mesenchymal stem cells in an experimental ocular hypertension model. Cytotherapy 2015, 17, 543–559. [Google Scholar] [CrossRef] [PubMed]
- Mead, B.; Berry, M.; Logan, A.; Scott, R.A.; Leadbeater, W.; Scheven, B.A. Stem cell treatment of degenerative eye disease. Stem Cell Res. 2015, 14, 243–257. [Google Scholar] [CrossRef] [Green Version]
- Rajashekhar, G. Mesenchymal stem cells: New players in retinopathy therapy. Front. Endocrinol. 2014, 5, 59. [Google Scholar] [CrossRef]
- Rajashekhar, G.; Ramadan, A.; Abburi, C.; Callaghan, B.; Traktuev, D.O.; Evans-Molina, C.; Maturi, R.; Harris, A.; Kern, T.S.; March, K.L. Regenerative therapeutic potential of adipose stromal cells in early stage diabetic retinopathy. PLoS ONE 2014, 9, e84671. [Google Scholar] [CrossRef]
- Mendel, T.A.; Clabough, E.B.; Kao, D.S.; Demidova-Rice, T.N.; Durham, J.T.; Zotter, B.C.; Seaman, S.A.; Cronk, S.M.; Rakoczy, E.P.; Katz, A.J.; et al. Pericytes derived from adipose-derived stem cells protect against retinal vasculopathy. PLoS ONE 2013, 8, e65691. [Google Scholar] [CrossRef]
- Ezquer, M.; Urzua, C.A.; Montecino, S.; Leal, K.; Conget, P.; Ezquer, F. Intravitreal administration of multipotent mesenchymal stromal cells triggers a cytoprotective microenvironment in the retina of diabetic mice. Stem Cell Res. Ther. 2016, 7, 42. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Yang, Z.; Li, K.; Yan, X.; Dong, F.; Zhao, C. Amelioration of diabetic retinopathy by engrafted human adipose-derived mesenchymal stem cells in streptozotocin diabetic rats. Graefes Arch. Clin. Exp. Ophthalmol. 2010, 248, 1415–1422. [Google Scholar] [CrossRef] [PubMed]
- Bunnell, B.A.; Flaat, M.; Gagliardi, C.; Patel, B.; Ripoll, C. Adipose-derived stem cells: Isolation, expansion and differentiation. Methods 2008, 45, 115–120. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bhatwadekar, A.D.; Duan, Y.; Korah, M.; Thinschmidt, J.S.; Hu, P.; Leley, S.P.; Caballero, S.; Shaw, L.; Busik, J.; Grant, M.B. Hematopoietic stem/progenitor involvement in retinal microvascular repair during diabetes: Implications for bone marrow rejuvenation. Vis. Res. 2017, 139, 211–220. [Google Scholar] [CrossRef] [PubMed]
- Duan, Y.; Beli, E.; Li Calzi, S.; Quigley, J.L.; Miller, R.C.; Moldovan, L.; Feng, D.; Salazar, T.E.; Hazra, S.; Al-Sabah, J.; et al. Loss of Angiotensin-Converting Enzyme 2 Exacerbates Diabetic Retinopathy by Promoting Bone Marrow Dysfunction. Stem Cells 2018, 36, 1430–1440. [Google Scholar] [CrossRef] [Green Version]
- Park, S.S.; Moisseiev, E.; Bauer, G.; Anderson, J.D.; Grant, M.B.; Zam, A.; Zawadzki, R.J.; Werner, J.S.; Nolta, J.A. Advances in bone marrow stem cell therapy for retinal dysfunction. Prog. Retin. Eye Res. 2017, 56, 148–165. [Google Scholar] [CrossRef] [PubMed]
- Park, S.S.; Caballero, S.; Bauer, G.; Shibata, B.; Roth, A.; Fitzgerald, P.G.; Forward, K.I.; Zhou, P.; McGee, J.; Telander, D.G.; et al. Long-term effects of intravitreal injection of GMP-grade bone-marrow-derived CD34+ cells in NOD-SCID mice with acute ischemia-reperfusion injury. Investig. Ophthalmol. Vis. Sci. 2012, 53, 986–994. [Google Scholar] [CrossRef] [PubMed]
- Bhatwadekar, A.D.; Guerin, E.P.; Jarajapu, Y.P.; Caballero, S.; Sheridan, C.; Kent, D.; Kennedy, L.; Lansang, M.C.; Ruscetti, F.W.; Pepine, C.J.; et al. Transient inhibition of transforming growth factor-beta1 in human diabetic CD34+ cells enhances vascular reparative functions. Diabetes 2010, 59, 2010–2019. [Google Scholar] [CrossRef]
- Moisseiev, E.; Smit-McBride, Z.; Oltjen, S.; Zhang, P.; Zawadzki, R.J.; Motta, M.; Murphy, C.J.; Cary, W.; Annett, G.; Nolta, J.A.; et al. Intravitreal Administration of Human Bone Marrow CD34+ Stem Cells in a Murine Model of Retinal Degeneration. Investig. Ophthalmol. Vis. Sci. 2016, 57, 4125–4135. [Google Scholar] [CrossRef]
- Chakravarthy, H.; Beli, E.; Navitskaya, S.; O’Reilly, S.; Wang, Q.; Kady, N.; Huang, C.; Grant, M.B.; Busik, J.V. Imbalances in Mobilization and Activation of Pro-Inflammatory and Vascular Reparative Bone Marrow-Derived Cells in Diabetic Retinopathy. PLoS ONE 2016, 11, e0146829. [Google Scholar] [CrossRef]
- Caballero, S.; Hazra, S.; Bhatwadekar, A.; Li Calzi, S.; Paradiso, L.J.; Miller, L.P.; Chang, L.J.; Kern, T.S.; Grant, M.B. Circulating mononuclear progenitor cells: Differential roles for subpopulations in repair of retinal vascular injury. Investig. Ophthalmol. Vis. Sci. 2013, 54, 3000–3009. [Google Scholar] [CrossRef] [PubMed]
- Cerman, E.; Akkoc, T.; Eraslan, M.; Sahin, O.; Ozkara, S.; Vardar Aker, F.; Subasi, C.; Karaoz, E.; Akkoc, T. Correction: Retinal Electrophysiological Effects of Intravitreal Bone Marrow Derived Mesenchymal Stem Cells in Streptozotocin Induced Diabetic Rats. PLoS ONE 2016, 11, e0165219. [Google Scholar] [CrossRef]
- Tzameret, A.; Sher, I.; Belkin, M.; Treves, A.J.; Meir, A.; Nagler, A.; Levkovitch-Verbin, H.; Barshack, I.; Rosner, M.; Rotenstreich, Y. Transplantation of human bone marrow mesenchymal stem cells as a thin subretinal layer ameliorates retinal degeneration in a rat model of retinal dystrophy. Exp. Eye Res. 2014, 118, 135–144. [Google Scholar] [CrossRef] [PubMed]
- Mead, B.; Logan, A.; Berry, M.; Leadbeater, W.; Scheven, B.A. Intravitreally transplanted dental pulp stem cells promote neuroprotection and axon regeneration of retinal ganglion cells after optic nerve injury. Investig. Ophthalmol. Vis. Sci. 2013, 54, 7544–7556. [Google Scholar] [CrossRef] [PubMed]
- Zhang, W.; Wang, Y.; Kong, J.; Dong, M.; Duan, H.; Chen, S. Therapeutic efficacy of neural stem cells originating from umbilical cord-derived mesenchymal stem cells in diabetic retinopathy. Sci. Rep. 2017, 7, 408. [Google Scholar] [CrossRef] [PubMed]
- Millan-Rivero, J.E.; Nadal-Nicolas, F.M.; Garcia-Bernal, D.; Sobrado-Calvo, P.; Blanquer, M.; Moraleda, J.M.; Vidal-Sanz, M.; Agudo-Barriuso, M. Human Wharton’s jelly mesenchymal stem cells protect axotomized rat retinal ganglion cells via secretion of anti-inflammatory and neurotrophic factors. Sci. Rep. 2018, 8, 16299. [Google Scholar] [CrossRef] [PubMed]
- Reid, E.; Guduric-Fuchs, J.; O’Neill, C.L.; Allen, L.D.; Chambers, S.E.J.; Stitt, A.W.; Medina, R.J. Preclinical Evaluation and Optimization of a Cell Therapy Using Human Cord Blood-Derived Endothelial Colony-Forming Cells for Ischemic Retinopathies. Stem Cells Transl. Med. 2018, 7, 59–67. [Google Scholar] [CrossRef] [PubMed]
- Kim, K.S.; Park, J.M.; Kong, T.; Kim, C.; Bae, S.H.; Kim, H.W.; Moon, J. Retinal Angiogenesis Effects of TGF-beta1 and Paracrine Factors Secreted From Human Placental Stem Cells in Response to a Pathological Environment. Cell Transplant. 2016, 25, 1145–1157. [Google Scholar] [CrossRef] [PubMed]
- Ryan, J.M.; Barry, F.P.; Murphy, J.M.; Mahon, B.P. Mesenchymal stem cells avoid allogeneic rejection. J. Inflamm. 2005, 2, 8. [Google Scholar] [CrossRef]
- De Becker, A.; Riet, I.V. Homing and migration of mesenchymal stromal cells: How to improve the efficacy of cell therapy? World J. Stem Cells 2016, 8, 73–87. [Google Scholar] [CrossRef]
- Noronha, N.C.; Mizukami, A.; Caliari-Oliveira, C.; Cominal, J.G.; Rocha, J.L.M.; Covas, D.T.; Swiech, K.; Malmegrim, K.C.R. Priming approaches to improve the efficacy of mesenchymal stromal cell-based therapies. Stem Cell Res. Ther. 2019, 10, 131. [Google Scholar] [CrossRef] [PubMed]
- Zhao, Y.; Zhang, H. Update on the mechanisms of homing of adipose tissue-derived stem cells. Cytotherapy 2016, 18, 816–827. [Google Scholar] [CrossRef] [PubMed]
- Periasamy, R.; Elshaer, S.L.; Gangaraju, R. CD140b (PDGFRβ) Signaling in Adipose-Derived Stem Cells Mediates Angiogenic Behavior of Retinal Endothelial Cells. Regen. Eng. Transl. Med. 2019, 5, 1–9. [Google Scholar] [CrossRef] [PubMed]
- Bourin, P.; Bunnell, B.A.; Casteilla, L.; Dominici, M.; Katz, A.J.; March, K.L.; Redl, H.; Rubin, J.P.; Yoshimura, K.; Gimble, J.M. Stromal cells from the adipose tissue-derived stromal vascular fraction and culture expanded adipose tissue-derived stromal/stem cells: A joint statement of the International Federation for Adipose Therapeutics and Science (IFATS) and the International Society for Cellular Therapy (ISCT). Cytotherapy 2013, 15, 641–648. [Google Scholar] [CrossRef]
- Ryu, Y.J.; Cho, T.J.; Lee, D.S.; Choi, J.Y.; Cho, J. Phenotypic characterization and in vivo localization of human adipose-derived mesenchymal stem cells. Mol. Cells 2013, 35, 557–564. [Google Scholar] [CrossRef] [PubMed]
- Baek, S.J.; Kang, S.K.; Ra, J.C. In vitro migration capacity of human adipose tissue-derived mesenchymal stem cells reflects their expression of receptors for chemokines and growth factors. Exp. Mol. Med. 2011, 43, 596–603. [Google Scholar] [CrossRef] [PubMed]
- Maumus, M.; Peyrafitte, J.A.; D’Angelo, R.; Fournier-Wirth, C.; Bouloumie, A.; Casteilla, L.; Sengenes, C.; Bourin, P. Native human adipose stromal cells: Localization, morphology and phenotype. Int. J. Obes. 2011, 35, 1141–1153. [Google Scholar] [CrossRef] [PubMed]
- Li Calzi, S.; Purich, D.L.; Chang, K.H.; Afzal, A.; Nakagawa, T.; Busik, J.V.; Agarwal, A.; Segal, M.S.; Grant, M.B. Carbon monoxide and nitric oxide mediate cytoskeletal reorganization in microvascular cells via vasodilator-stimulated phosphoprotein phosphorylation: Evidence for blunted responsiveness in diabetes. Diabetes 2008, 57, 2488–2494. [Google Scholar] [CrossRef]
- Farhang, N.; Brunger, J.M.; Stover, J.D.; Thakore, P.I.; Lawrence, B.; Guilak, F.; Gersbach, C.A.; Setton, L.A.; Bowles, R.D. (*) CRISPR-Based Epigenome Editing of Cytokine Receptors for the Promotion of Cell Survival and Tissue Deposition in Inflammatory Environments. Tissue Eng. Part A 2017, 23, 738–749. [Google Scholar] [CrossRef] [PubMed]
- Park, T.S.; Bhutto, I.; Zimmerlin, L.; Huo, J.S.; Nagaria, P.; Miller, D.; Rufaihah, A.J.; Talbot, C.; Aguilar, J.; Grebe, R.; et al. Vascular progenitors from cord blood-derived induced pluripotent stem cells possess augmented capacity for regenerating ischemic retinal vasculature. Circulation 2014, 129, 359–372. [Google Scholar] [CrossRef]
- Bhattacharya, S.; Gangaraju, R.; Chaum, E. Recent Advances in Retinal Stem Cell Therapy. Curr. Mol. Biol. Rep. 2017, 3, 172–182. [Google Scholar] [CrossRef] [PubMed]
- Hajmousa, G.; Elorza, A.A.; Nies, V.J.; Jensen, E.L.; Nagy, R.A.; Harmsen, M.C. Hyperglycemia Induces Bioenergetic Changes in Adipose-Derived Stromal Cells While Their Pericytic Function Is Retained. Stem Cells Dev. 2016, 25, 1444–1453. [Google Scholar] [CrossRef] [PubMed]
- Elshaer, S.L.; Evans, W.; Pentecost, M.; Lenin, R.; Periasamy, R.; Jha, K.A.; Alli, S.; Gentry, J.; Thomas, S.M.; Sohl, N.; et al. Adipose stem cells and their paracrine factors are therapeutic for early retinal complications of diabetes in the Ins2(Akita) mouse. Stem Cell Res. Ther. 2018, 9, 322. [Google Scholar] [CrossRef] [PubMed]
- Mehrbani Azar, Y.; Green, R.; Niesler, C.U.; van de Vyver, M. Antioxidant Preconditioning Improves the Paracrine Responsiveness of Bone Marrow Mesenchymal Stem Cells to Diabetic Wound Fluid. Stem Cells Dev. 2018. [Google Scholar] [CrossRef] [PubMed]
- Yang, Y.; Choi, H.; Seon, M.; Cho, D.; Bang, S.I. LL-37 stimulates the functions of adipose-derived stromal/stem cells via early growth response 1 and the MAPK pathway. Stem Cell Res. Ther. 2016, 7, 58. [Google Scholar] [CrossRef] [PubMed]
- Kuriyan, A.E.; Albini, T.A.; Townsend, J.H.; Rodriguez, M.; Pandya, H.K.; Leonard, R.E., 2nd; Parrott, M.B.; Rosenfeld, P.J.; Flynn, H.W., Jr.; Goldberg, J.L. Vision Loss after Intravitreal Injection of Autologous “Stem Cells” for AMD. N. Engl. J. Med. 2017, 376, 1047–1053. [Google Scholar] [CrossRef] [PubMed]
- Nirwan, R.S.; Albini, T.A.; Sridhar, J.; Flynn, H.W., Jr.; Kuriyan, A.E. Assessing “Cell Therapy” Clinics Offering Treatments of Ocular Conditions using Direct-to-Consumer Marketing Websites in the United States. Ophthalmology 2019, 126, 1350–1355. [Google Scholar] [CrossRef] [PubMed]
- Gu, X.; Yu, X.; Zhao, C.; Duan, P.; Zhao, T.; Liu, Y.; Li, S.; Yang, Z.; Li, Y.; Qian, C.; et al. Efficacy and Safety of Autologous Bone Marrow Mesenchymal Stem Cell Transplantation in Patients with Diabetic Retinopathy. Cell Physiol. Biochem. 2018, 49, 40–52. [Google Scholar] [CrossRef] [PubMed]
- Hajmousa, G.; Przybyt, E.; Pfister, F.; Paredes-Juarez, G.A.; Moganti, K.; Busch, S.; Kuipers, J.; Klaassen, I.; van Luyn, M.J.A.; Krenning, G.; et al. Human adipose tissue-derived stromal cells act as functional pericytes in mice and suppress high-glucose-induced proinflammatory activation of bovine retinal endothelial cells. Diabetologia 2018, 61, 2371–2385. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Cronk, S.M.; Kelly-Goss, M.R.; Ray, H.C.; Mendel, T.A.; Hoehn, K.L.; Bruce, A.C.; Dey, B.K.; Guendel, A.M.; Tavakol, D.N.; Herman, I.M.; et al. Adipose-derived stem cells from diabetic mice show impaired vascular stabilization in a murine model of diabetic retinopathy. Stem Cells Transl. Med. 2015, 4, 459–467. [Google Scholar] [CrossRef]
- Ji, J.; Zhang, D.; Wei, W.; Shen, B.; Zhang, Y.; Wang, Y.; Tang, Z.; Ni, N.; Sun, H.; Liu, J.; et al. Decellularized matrix of adipose-derived mesenchymal stromal cells enhanced retinal progenitor cell proliferation via the Akt/Erk pathway and neuronal differentiation. Cytotherapy 2018, 20, 74–86. [Google Scholar] [CrossRef] [PubMed]
- Ezati, R.; Etemadzadeh, A.; Soheili, Z.S.; Samiei, S.; Ranaei Pirmardan, E.; Davari, M.; Najafabadi, H.S. The influence of rAAV2-mediated SOX2 delivery into neonatal and adult human RPE cells; a comparative study. J. Cell Physiol. 2018, 233, 1222–1235. [Google Scholar] [CrossRef] [PubMed]
- Kern, T.S.; Antonetti, D.A.; Smith, L.E.H. Pathophysiology of Diabetic Retinopathy: Contribution and Limitations of Laboratory Research. Ophthalmic Res. 2019, 1–7. [Google Scholar] [CrossRef] [PubMed]
- Yeltokova, M.; Ulyanova, O.; Askarov, M.; Chernyshova, A.; Kozina, L. Integral Hematologic Indices in the Evaluation of the Immunologic Reactivity of the Organism in a Patient With Complication of Type 1 Diabetes Mellitus: A Case of Diabetic Retinopathy After Autologous Mesenchymal Stem Cell Transplant. Exp. Clin. Transplant. 2019, 17, 234–235. [Google Scholar] [CrossRef]
- Achberger, K.; Haderspeck, J.C.; Kleger, A.; Liebau, S. Stem cell-based retina models. Adv. Drug Deliv. Rev. 2019, 140, 33–50. [Google Scholar] [CrossRef]
© 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Gaddam, S.; Periasamy, R.; Gangaraju, R. Adult Stem Cell Therapeutics in Diabetic Retinopathy. Int. J. Mol. Sci. 2019, 20, 4876. https://doi.org/10.3390/ijms20194876
Gaddam S, Periasamy R, Gangaraju R. Adult Stem Cell Therapeutics in Diabetic Retinopathy. International Journal of Molecular Sciences. 2019; 20(19):4876. https://doi.org/10.3390/ijms20194876
Chicago/Turabian StyleGaddam, Sriprachodaya, Ramesh Periasamy, and Rajashekhar Gangaraju. 2019. "Adult Stem Cell Therapeutics in Diabetic Retinopathy" International Journal of Molecular Sciences 20, no. 19: 4876. https://doi.org/10.3390/ijms20194876