PMID- 33661042
OWN - NLM
STAT- MEDLINE
DCOM- 20220103
LR  - 20220103
IS  - 1557-7732 (Electronic)
IS  - 1080-7683 (Linking)
VI  - 37
IP  - 5
DP  - 2021 Jun
TI  - Neurotrophic Factors Secreted by Induced Pluripotent Stem Cell-Derived Retinal 
      Progenitors Promote Retinal Survival and Preservation in an Adult Porcine 
      Neuroretina Model.
PG  - 301-312
LID - 10.1089/jop.2020.0088 [doi]
AB  - Purpose: Paracrine factors released by pluripotent stem cells have shown great 
      potential as therapeutic agents in regenerative medicine. The purpose of this 
      study was to characterize trophic factor secretion of retinal progenitor cells 
      (RPCs) derived from human induced pluripotent stem cells (iPSCs) and to assess 
      its impact on retinal survival ex vivo. Methods: RPCs were generated from human 
      3D1 iPSCs following previously established protocols with modifications. 
      Conditioned medium (CM) was harvested from iPSC-derived retinal progenitors and 
      analyzed for trophic factor composition through multiplex enzyme-linked 
      immunosorbent assay. Retina-preserving capability of the collected CM was 
      examined using a degenerative porcine neuroretina model. Viability of the 
      CM-treated retina explants was evaluated using the resazurin-based PrestoBlue 
      reagent, whereas the lactate dehydrogenase (LDH) assay was used to assess retinal 
      cytotoxicity. Retina explants were also analyzed morphologically through 
      immunohistochemistry for glial cell activation and apoptosis. Results: We have 
      successfully generated and characterized iPSC-derived RPCs that secreted an array 
      of neuroprotective factors, including osteopontin, hepatocyte growth factor, 
      stromal cell-derived factor 1, and insulin-like growth factor-1. Retina explants 
      cultured in CM derived from iPSC-RPCs (iPSC-RPC-CM) showed better preservation of 
      the retinal microarchitecture and fewer terminal deoxynucleotidyl transferase 
      dUTP nick-end labeling (TUNEL)(+) nuclei, and reduced reactive gliosis. 
      Furthermore, we saw a reduction in extracellular LDH levels in CM-treated retina 
      explants, which also exhibited higher metabolic activity than the untreated 
      controls. Conclusions: iPSC-derived RPCs secrete many trophic factors that have 
      been shown to promote neuroprotection, tissue repair, and regeneration in the 
      retina. Overall, we have demonstrated the neuroprotective effects of iPSC-RPC-CM 
      through a degenerative neuroretina model ex vivo.
FAU - Rettinger, Christina L
AU  - Rettinger CL
AD  - Ocular and Sensory Trauma Task Area, United States Army Institute of Surgical 
      Research, Fort Sam Houston, Texas, USA.
FAU - Kaini, Ramesh R
AU  - Kaini RR
AD  - Ocular and Sensory Trauma Task Area, United States Army Institute of Surgical 
      Research, Fort Sam Houston, Texas, USA.
FAU - Burke, Teresa A
AU  - Burke TA
AD  - Ocular and Sensory Trauma Task Area, United States Army Institute of Surgical 
      Research, Fort Sam Houston, Texas, USA.
FAU - Wang, Heuy-Ching
AU  - Wang HC
AD  - Ocular and Sensory Trauma Task Area, United States Army Institute of Surgical 
      Research, Fort Sam Houston, Texas, USA.
LA  - eng
PT  - Journal Article
DEP - 20210303
PL  - United States
TA  - J Ocul Pharmacol Ther
JT  - Journal of ocular pharmacology and therapeutics : the official journal of the 
      Association for Ocular Pharmacology and Therapeutics
JID - 9511091
RN  - 0 (Nerve Growth Factors)
RN  - 0 (Neuroprotective Agents)
RN  - EC 1.1.1.27 (L-Lactate Dehydrogenase)
SB  - IM
MH  - Adult
MH  - Animals
MH  - Apoptosis
MH  - Cell Survival
MH  - Enzyme-Linked Immunosorbent Assay/methods
MH  - Female
MH  - Humans
MH  - Immunohistochemistry/methods
MH  - Induced Pluripotent Stem Cells/*metabolism/transplantation
MH  - L-Lactate Dehydrogenase/drug effects/metabolism
MH  - Models, Animal
MH  - Nerve Growth Factors/*pharmacology
MH  - Neuroglia/drug effects/pathology
MH  - Neuroprotective Agents/*pharmacology
MH  - Regenerative Medicine/statistics & numerical data
MH  - Retina/*drug effects/embryology/pathology/ultrastructure
MH  - Stem Cells/metabolism
MH  - Swine
OTO - NOTNLM
OT  - human iPSCs
OT  - neuroprotection
OT  - porcine retina explants
OT  - retinal progenitor cells
OT  - retinal survival
EDAT- 2021/03/05 06:00
MHDA- 2022/01/04 06:00
CRDT- 2021/03/04 12:11
PHST- 2021/03/05 06:00 [pubmed]
PHST- 2022/01/04 06:00 [medline]
PHST- 2021/03/04 12:11 [entrez]
AID - 10.1089/jop.2020.0088 [doi]
PST - ppublish
SO  - J Ocul Pharmacol Ther. 2021 Jun;37(5):301-312. doi: 10.1089/jop.2020.0088. Epub 
      2021 Mar 3.