PMID- 37639051
OWN - NLM
STAT- MEDLINE
DCOM- 20230829
LR  - 20231003
IS  - 1573-4838 (Electronic)
IS  - 0957-4530 (Print)
IS  - 0957-4530 (Linking)
VI  - 34
IP  - 9
DP  - 2023 Aug 28
TI  - Enhanced therapeutic effects of mesenchymal stem cell-derived extracellular 
      vesicles within chitosan hydrogel in the treatment of diabetic foot ulcers.
PG  - 43
LID - 10.1007/s10856-023-06746-y [doi]
LID - 43
AB  - Extracellular vesicles (EVs) derived from human umbilical cord mesenchymal stem 
      cells (hUCMSCs) have emerged as promising candidates for cell-free therapy in 
      various diseases, including chronic cutaneous wounds. However, the lack of 
      standardized protocols for EVs' preparation and identification poses a 
      significant challenge to their clinical application. Thus, the objective was to 
      develop a safe and efficient method for the large-scale production of 
      hUCMSC-derived EVs while establishing a comprehensive identification protocol 
      encompassing morphology, particle size distribution, protein expression, and 
      purity. This study observed that most of the EVs acquired through the protocol 
      exhibited either a cup-shaped or round-shaped structure, with a median diameter 
      of ~73.25 nm. The proportions of EVs positive for CD9, CD63, and CD81 were 37.5%, 
      38.6%, and 19.8%, respectively. To enhance their therapeutic potential in wound 
      treatment, EVs were incorporated into chitosan hydrogel, forming chitosan 
      hydrogel-EVs (CS-EVs). Furthermore, it was demonstrated that CS-EVs exhibited 
      continuous release of EVs into the surrounding environment and, importantly, that 
      the released EVs were internalized by human umbilical vein endothelial cells 
      (HUVECs), resulting in significant enhancement of cell migration and 
      angiogenesis. Additionally, in a rat model of diabetic foot ulcers, CS-EVs 
      demonstrated a robust therapeutic effect in promoting wound healing. Following a 
      15-day treatment period, the group treated with CS-EVs demonstrated an impressive 
      93.3% wound closure ability, accompanied by a high degree of 
      re-epithelialization. In contrast, the control group exhibited only a 71.5% 
      reduction in wound size. In summary, this study offers solutions for the 
      purification, characterization, and application of EVs in clinical wound 
      treatment. These results not only offer fresh perspectives on the involvement of 
      hUCMSC-derived EVs in wound healing but also introduce a non-invasive approach 
      for applying EVs that holds practical significance in skin repair.
CI  - (c) 2023. The Author(s).
FAU - Yang, Shuangshuang
AU  - Yang S
AD  - Qilu Cell Therapy Technology Co., Ltd, No.1758 Gangyuan Six Road, Ji'nan, 
      Shandong, China.
FAU - Chen, Siyu
AU  - Chen S
AD  - Qilu Cell Therapy Technology Co., Ltd, No.1758 Gangyuan Six Road, Ji'nan, 
      Shandong, China.
FAU - Zhang, Chengpeng
AU  - Zhang C
AD  - Qilu Cell Therapy Technology Co., Ltd, No.1758 Gangyuan Six Road, Ji'nan, 
      Shandong, China.
FAU - Han, Jing
AU  - Han J
AD  - Qilu Cell Therapy Technology Co., Ltd, No.1758 Gangyuan Six Road, Ji'nan, 
      Shandong, China.
FAU - Lin, Chunyuan
AU  - Lin C
AD  - Qilu Cell Therapy Technology Co., Ltd, No.1758 Gangyuan Six Road, Ji'nan, 
      Shandong, China.
FAU - Zhao, Xiaohui
AU  - Zhao X
AD  - Qilu Cell Therapy Technology Co., Ltd, No.1758 Gangyuan Six Road, Ji'nan, 
      Shandong, China.
FAU - Guo, Huizhen
AU  - Guo H
AD  - Qilu Cell Therapy Technology Co., Ltd, No.1758 Gangyuan Six Road, Ji'nan, 
      Shandong, China.
FAU - Tan, Yi
AU  - Tan Y
AD  - Qilu Cell Therapy Technology Co., Ltd, No.1758 Gangyuan Six Road, Ji'nan, 
      Shandong, China. pkuty@126.com.
LA  - eng
GR  - 2021YFA1101502/Ministry of Science and Technology of the People's Republic of 
      China/
GR  - ZR2021QC202/Natural Science Foundation of Shandong Province/
PT  - Journal Article
DEP - 20230828
PL  - United States
TA  - J Mater Sci Mater Med
JT  - Journal of materials science. Materials in medicine
JID - 9013087
RN  - 0 (Hydrogels)
RN  - 9012-76-4 (Chitosan)
SB  - IM
MH  - Humans
MH  - Animals
MH  - Rats
MH  - *Diabetic Foot/therapy
MH  - Hydrogels
MH  - *Chitosan
MH  - *Extracellular Vesicles
MH  - Human Umbilical Vein Endothelial Cells
MH  - *Mesenchymal Stem Cells
MH  - *Diabetes Mellitus
PMC - PMC10462522
COIS- The authors declare no competing interests.
EDAT- 2023/08/28 12:43
MHDA- 2023/08/29 12:44
PMCR- 2023/08/28
CRDT- 2023/08/28 11:06
PHST- 2023/04/27 00:00 [received]
PHST- 2023/08/09 00:00 [accepted]
PHST- 2023/08/29 12:44 [medline]
PHST- 2023/08/28 12:43 [pubmed]
PHST- 2023/08/28 11:06 [entrez]
PHST- 2023/08/28 00:00 [pmc-release]
AID - 10.1007/s10856-023-06746-y [pii]
AID - 6746 [pii]
AID - 10.1007/s10856-023-06746-y [doi]
PST - epublish
SO  - J Mater Sci Mater Med. 2023 Aug 28;34(9):43. doi: 10.1007/s10856-023-06746-y.