PMID- 36660688
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230121
IS  - 2305-5839 (Print)
IS  - 2305-5847 (Electronic)
IS  - 2305-5839 (Linking)
VI  - 10
IP  - 24
DP  - 2022 Dec
TI  - BDNF-overexpressing MSCs delivered by hydrogel in acute ischemic stroke 
      treatment.
PG  - 1393
LID - 10.21037/atm-22-5921 [doi]
LID - 1393
AB  - BACKGROUND: Ischemic stroke treatment is a challenge worldwide. The efficacy and 
      safety of mesenchymal stem cells (MSCs) for stroke have been confirmed. However, 
      poor survival of MSCs in the ischemic environment limits the therapy efficacy. 
      Changes in MSC status in the ischemic environment after transplantation is 
      difficult to monitor. This study aimed to deliver brain-derived neurotrophic 
      factor (BDNF)-overexpressing MSCs by hydrogel (H-B-MSCs) to promote recovery 
      after ischemic stroke. METHODS: MSCs were transfected with lentivirus carrying 
      luc2 and BDNF cassette. The properties of hydrogel were tested after synthesis 
      with thiolated gelatin (Gel-SH), thiolated hyaluronic acid (HA-SH), and 
      polyethylene glycol diacrylate (PEGDA). Oxygen-glucose deprivation (OGD) test was 
      carried out to confirm the protective effects of hydrogel in the ischemic 
      environment. Three days after stroke induction, H-B-MSCs, hydrogel carrying MSCs 
      (H-MSCs), or phosphate-buffered saline (PBS) was injected into the brains of 
      mice, respectively. Bioluminescence imaging (BLI) was performed at 3, 7, 14, and 
      21 days post-cell-transplantation to monitor the dynamic status of MSCs. In the 
      meantime, histology, quantitative polymerase chain reaction (qPCR), enzyme-linked 
      immunosorbent assay (ELISA), western blot, and behavior tests were carried out at 
      different time points. RESULTS: Hydrogel with good biocompatibility was 
      synthesized. Lentivirus transfection significantly increased the expression of 
      BDNF. BDNF-MSCs could be tracked by BLI in vitro. In vitro OGD/reperfusion 
      (OGD/R) test results suggested that MSCs carried by hydrogel could survive longer 
      in an environment with low oxygen and glucose. H-B-MSCs significantly improved 
      functional recovery after ischemic stroke. Furthermore, H-B-MSCs treatment 
      promoted neurogenesis, white matter recovery, and angiogenesis after ischemic 
      stroke. MSC dynamics could be monitored in vivo with BLI. CONCLUSIONS: We 
      effectively established a robust MSC delivery system with hydrogel. Prolonged 
      survival of transplanted BDNF-MSCs with a hydrogel delivery system could promote 
      the recovery of ischemic stroke via the continuous release of BDNF.
CI  - 2022 Annals of Translational Medicine. All rights reserved.
FAU - Wang, Congxiao
AU  - Wang C
AD  - Department of Interventional Medical Center, the Affiliated Hospital of Qingdao 
      University, Qingdao, China.
FAU - Tian, Chuan
AU  - Tian C
AD  - Department of Interventional Medical Center, the Affiliated Hospital of Qingdao 
      University, Qingdao, China.
FAU - Cai, Duo
AU  - Cai D
AD  - Medical Animal Lab, Medical Research Center, the Affiliated Hospital of Qingdao 
      University, Qingdao, China.
FAU - Jiang, Han
AU  - Jiang H
AD  - Department of Interventional Medical Center, the Affiliated Hospital of Qingdao 
      University, Qingdao, China.
FAU - Zhang, Wei
AU  - Zhang W
AD  - Department of Interventional Medical Center, the Affiliated Hospital of Qingdao 
      University, Qingdao, China.
FAU - Liu, Shifeng
AU  - Liu S
AD  - Department of Interventional Medical Center, the Affiliated Hospital of Qingdao 
      University, Qingdao, China.
FAU - Peng, Lijing
AU  - Peng L
AD  - Department of Clinical Laboratory, the Affiliated Hospital of Qingdao University, 
      Qingdao, China.
FAU - Hu, Xiaokun
AU  - Hu X
AD  - Department of Interventional Medical Center, the Affiliated Hospital of Qingdao 
      University, Qingdao, China.
LA  - eng
PT  - Journal Article
PL  - China
TA  - Ann Transl Med
JT  - Annals of translational medicine
JID - 101617978
PMC - PMC9843400
OTO - NOTNLM
OT  - BDNF-overexpressing MSCs by hydrogel (H-B-MSCs)
OT  - Mesenchymal stem cells (MSCs)
OT  - brain-derived neurotrophic factor-overexpressing (BDNF-overexpressing)
COIS- Conflicts of Interest: All authors have completed the ICMJE uniform disclosure 
      form (available at 
      https://atm.amegroups.com/article/view/10.21037/atm-22-5921/coif). The authors 
      have no conflicts of interest to declare.
EDAT- 2023/01/21 06:00
MHDA- 2023/01/21 06:01
PMCR- 2022/12/01
CRDT- 2023/01/20 02:16
PHST- 2022/11/03 00:00 [received]
PHST- 2022/12/19 00:00 [accepted]
PHST- 2023/01/20 02:16 [entrez]
PHST- 2023/01/21 06:00 [pubmed]
PHST- 2023/01/21 06:01 [medline]
PHST- 2022/12/01 00:00 [pmc-release]
AID - atm-10-24-1393 [pii]
AID - 10.21037/atm-22-5921 [doi]
PST - ppublish
SO  - Ann Transl Med. 2022 Dec;10(24):1393. doi: 10.21037/atm-22-5921.