title: Perivascular Progenitor Cells Derived From Human Embryonic Stem Cells Exhibit Functional Characteristics of Pericytes and Improve the Retinal Vasculature in a Rodent Model of Diabetic Retinopathy.
abstract: : Diabetic retinopathy (DR) is the leading cause of blindness in working-age people. Pericyte loss is one of the pathologic cellular events in DR, which weakens the retinal microvessels. Damage to the microvascular networks is irreversible and permanent; thus further progression of DR is inevitable. In this study, we hypothesize that multipotent perivascular progenitor cells derived from human embryonic stem cells (hESC-PVPCs) improve the damaged retinal vasculature in the streptozotocin-induced diabetic rodent models. We describe a highly efficient and feasible protocol to derive such cells with a natural selection method without cell-sorting processes. As a cellular model of pericytes, hESC-PVPCs exhibited marker expressions such as CD140B, CD146, NG2, and functional characteristics of pericytes. Following a single intravitreal injection into diabetic Brown Norway rats, we demonstrate that the cells localized alongside typical perivascular regions of the retinal vasculature and stabilized the blood-retinal barrier breakdown. Findings in this study highlight a therapeutic potential of hESC-PVPCs in DR by mimicking the role of pericytes in vascular stabilization.
  
  
  
  This study provides a simple and feasible method to generate perivascular progenitor cells from human embryonic stem cells. These cells share functional characteristics with pericytes, which are irreversibly lost at the onset of diabetic retinopathy. Animal studies demonstrated that replenishing the damaged pericytes with perivascular progenitor cells could restore retinal vascular integrity and prevent fluid leakage. This provides promising and compelling evidence that perivascular progenitor cells can be used as a novel therapeutic agent to treat diabetic retinopathy patients.
authors.affiliation: Department of Tissue Morphogenesis, Max-Planck Institute for Molecular Biomedicine, Münster, Germany.
authors.forename: Jung Mo
authors.initials: JM
authors.lastname: Kim
authors.affiliation: Stem Cell Research Lab, Department of Stem Cell Biology, School of Medicine, Konkuk University, Seoul, Republic of Korea.
authors.forename: Ki-Sung
authors.initials: KS
authors.lastname: Hong
authors.affiliation: Department of Ophthalmology, CHA Bundang Medical Center, CHA University, Seongnam, Republic of Korea.
authors.forename: Won Kyung
authors.initials: WK
authors.lastname: Song
authors.affiliation: Stem Cell Research Lab, Department of Stem Cell Biology, School of Medicine, Konkuk University, Seoul, Republic of Korea.
authors.forename: Daekyeong
authors.initials: D
authors.lastname: Bae
authors.affiliation: Stem Cell Research Lab, Department of Stem Cell Biology, School of Medicine, Konkuk University, Seoul, Republic of Korea.
authors.forename: In-Kyu
authors.initials: IK
authors.lastname: Hwang
authors.affiliation: Stem Cell Research Lab, Department of Stem Cell Biology, School of Medicine, Konkuk University, Seoul, Republic of Korea.
authors.forename: Jong Soo
authors.initials: JS
authors.lastname: Kim
authors.affiliation: Stem Cell Research Lab, Department of Stem Cell Biology, School of Medicine, Konkuk University, Seoul, Republic of Korea hmchung@kku.ac.kr.
authors.forename: Hyung-Min
authors.initials: HM
authors.lastname: Chung
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques / Q000379:methods; D002454:Cell Differentiation; D003921:Diabetes Mellitus, Experimental / Q000473:pathology; D003930:Diabetic Retinopathy / Q000473:pathology*; D004195:Disease Models, Animal; D000066449:Human Embryonic Stem Cells / Q000166:cytology* / Q000637:transplantation*; D006801:Humans; D039902:Multipotent Stem Cells; D020411:Oligonucleotide Array Sequence Analysis; D020286:Pericytes / Q000166:cytology*; D051381:Rats
keywords: Blood-retinal barrier; Diabetic retinopathy; Human embryonic stem cells; Pericytes; Perivascular progenitor cells