MSCs Deliver Hypoxia‐Treated Mitochondria Reprogramming Acinar Metabolism to Alleviate Severe Acute Pancreatitis Injury

Mitochondrial function impairment due to abnormal opening of the mitochondrial permeability transition pore (MPTP) is considered the central event in acute pancreatitis; however, therapeutic choices for this condition remain controversial. Mesenchymal stem cells (MSCs) are a family member of stem ce...

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Bibliographic Details
Published in:Advanced science 2023-09, Vol.10 (25), p.e2207691-n/a
Main Authors: Hu, Zhengyu, Wang, Dongyan, Gong, Jian, Li, Yan, Ma, Zhilong, Luo, Tingyi, Jia, Xuyang, Shi, Yihai, Song, Zhenshun
Format: Article
Language:English
Subjects:
Adenosine triphosphate
Autophagy
cargocytes
Clinical trials
Endoplasmic reticulum
Hypoxia
Inflammation
Inflammatory diseases
mesenchymal stem cells
metabolic reprogramming
Metabolism
Metabolites
Mitochondria
mitochondria transfer
Neutrophils
Pancreas
Pancreatitis
severe acute pancreatitis
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Summary:Mitochondrial function impairment due to abnormal opening of the mitochondrial permeability transition pore (MPTP) is considered the central event in acute pancreatitis; however, therapeutic choices for this condition remain controversial. Mesenchymal stem cells (MSCs) are a family member of stem cells with immunomodulatory and anti‐inflammatory capabilities that can mitigate damage in experimental pancreatitis. Here, it is shown that MSCs deliver hypoxia‐treated functional mitochondria to damaged pancreatic acinar cells (PACs) via extracellular vesicles (EVs), which reverse the metabolic function of PACs, maintain ATP supply, and exhibit an excellent injury‐inhibiting effect. Mechanistically, hypoxia inhibits superoxide accumulation in the mitochondria of MSCs and upregulates the membrane potential, which is internalized into PACs via EVs, thus, remodeling the metabolic state. In addition, cargocytes constructed via stem cell denucleation as mitochondrial vectors are shown to exert similar therapeutic effects to MSCs. These findings reveal an important mechanism underlying the role of mitochondria in MSC therapy and offer the possibility of applying mitochondrial therapy to patients with severe acute pancreatitis. MSCs deliver hypoxia‐treated functional mitochondria to pancreatic acinar cells (PACs) via extracellular vesicles (EVs), which reprogram the metabolic state of PACs, maintain ATP supply, and exhibit an excellent injury‐inhibiting effect. In addition, Cargocytes constructed via stem cell denucleation as mitochondrial carriers show excellent therapeutic effects in vivo.
ISSN:2198-3844
2198-3844
DOI:10.1002/advs.202207691