In situ transplantation of adipose-derived stem cells via photoactivation improves glucose metabolism in obese mice

Zhu, Luochen; Feng, Ziqian; Shu, Xin; Gao, Qian; Wu, Jiaqi; Du, Zuoqin; Li, Rong; Wang, Liqun; Chen, Ni; Li, Yang; Luo, Mao; Wu, Jianbo

doi:10.1186/s13287-021-02494-4

Cited by 9 publications

(6 citation statements)

References 30 publications

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“…Cells were cultured in 37 °C at 5% CO2 and 20% O 2 incubator. Flow cytometry is used to identify the ASCs with surface markers as described previously by us [ 10 , 11 ]. Briefly, ASCs are positive CD29 (BD Pharmingen), CD90 (BD Pharmingen), and CD105 (Biolegend) in a normal conditional and light treatment.…”

Section: Methodsmentioning

confidence: 99%

Photomodulation alleviates cellular senescence of aging adipose-derived stem cells

Zhang

Shu

et al. 2023

Cell Commun Signal

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Background Mesenchymal stem cells (MSCs) therapies are emerging as a promising approach to therapeutic regeneration. Therapeutic persistence and reduced functional stem cells following cell delivery remain critical hurdles for clinical investigation due to the senescence of freshly isolated cells and extensive in-vitro passage. Methods Cultured adipose-derived stem cells (ASCs) were derived from subcutaneous white adipose tissue isolated from mice fed a normal diet. We performed senescence-associated-β-galactosidase (SA-β-gal) staining, real-time PCR, and Westernblot to evaluate the levels related to cellular senescence markers. Results The mRNA expression levels of senescence markers were significantly increased in the later passage of ASCs. We show that light activation reduced the expression of senescent genes, and SA-β-Gal in all cells at passages. Moreover, the light-activated ASCs-derived exosomes decrease the expression of senescence, and SA-β-Gal in the later passage cells. We further investigated the photoreceptive effect of Opsin3 (Opn3) in light-activated ASCs. Deletion of Opn3 abolished the differences of light activation in reduced expression of senescent genes, increased Ca 2+ influx, and cAMP levels. Conclusions ASCs can undergo cellular senescence in-vitro passage. Photomodulation might be better preserved over senescence and Opn3-dependent activation in aged ASCs. Light-activated ASCs-derived exosomes could be served as e a new protective paradigm for cellular senescence in-vitro passage.

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Section: Methodsmentioning

confidence: 99%

Photomodulation alleviates cellular senescence of aging adipose-derived stem cells

Zhang

Shu

et al. 2023

Cell Commun Signal

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“…When obese MSCs were administered at the onset of disease there was a higher total lesion area in the spinal cord compared to vehicle treated controls. In addition, lean MSCs but not obese MSCs protected against ischemic injury, reducing renal atrophy and alleviating renovascular hypertension in mouse models of renal artery stenosis (94,114,115). Therefore, both in vitro and in vivo analyses of immunomodulatory behaviour in MSCs isolated from patients with metabolic disease support a compromised immunomodulatory phenotype (Tables 2, 3).…”

Section: Therapeutic Efficacy Of Obese Mscsmentioning

confidence: 98%

“…Additional positive effects on the systemic manifestations of metabolic syndrome have been described. Intramuscular injection of human atMSCs ( 90 ), injection of murine atMSCs into visceral epididymal adipose tissue ( 94 ), and intraperitoneal injection of human amniotic MSC CM ( 92 ) all significantly decreased blood glucose levels and improved insulin sensitivity. The human and murine atMSCs further caused a significant drop in serum triglyceride levels ( 90 , 94 ) which has the potential of being cardioprotective ( 96 ).…”

Section: The Effect Of Obesity On Mesenchymal Stromal Cellsmentioning

confidence: 99%

“…Intramuscular injection of human atMSCs ( 90 ), injection of murine atMSCs into visceral epididymal adipose tissue ( 94 ), and intraperitoneal injection of human amniotic MSC CM ( 92 ) all significantly decreased blood glucose levels and improved insulin sensitivity. The human and murine atMSCs further caused a significant drop in serum triglyceride levels ( 90 , 94 ) which has the potential of being cardioprotective ( 96 ). Human amniotic atMSC CM led to increased energy expenditure, elevated thermogenesis, and inhibited adipogenesis by suppressing the expression of genes required for the differentiation of pre-adipocytes.…”

Section: The Effect Of Obesity On Mesenchymal Stromal Cellsmentioning

confidence: 99%

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Translating MSC Therapy in the Age of Obesity

et al. 2022

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Mesenchymal stromal cell (MSC) therapy has seen increased attention as a possible option to treat a number of inflammatory conditions including COVID-19 acute respiratory distress syndrome (ARDS). As rates of obesity and metabolic disease continue to rise worldwide, increasing proportions of patients treated with MSC therapy will be living with obesity. The obese environment poses critical challenges for immunomodulatory therapies that should be accounted for during development and testing of MSCs. In this review, we look to cancer immunotherapy as a model for the challenges MSCs may face in obese environments. We then outline current evidence that obesity alters MSC immunomodulatory function, drastically modifies the host immune system, and therefore reshapes interactions between MSCs and immune cells. Finally, we argue that obese environments may alter essential features of allogeneic MSCs and offer potential strategies for licensing of MSCs to enhance their efficacy in the obese microenvironment. Our aim is to combine insights from basic research in MSC biology and clinical trials to inform new strategies to ensure MSC therapy is effective for a broad range of patients.

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“…The 8-week-old male C57BL/6J mice were fed with a HFD (fat 60%, carbohydrate 25% and protein 15%) for 16 weeks, as described previously [33,34]. Age-matched male mice fed with a normal chow diet (fat 10%, carbohydrate 75% and protein 15%) were used as controls.…”

Section: Hfd-fed Mouse Modelmentioning

confidence: 99%

Glycation of Tie-2 Inhibits Angiopoietin-1 Signaling Activation and Angiopoietin-1-Induced Angiogenesis

Zhou

Chen

et al. 2022

IJMS

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The impairment of the angiopoietin-1 (Ang-1)/Tie-2 signaling pathway has been thought to play a critical role in diabetic complications. However, the underlying mechanisms remain unclear. The present study aims to investigate the effects of Tie-2 glycation on Ang-1 signaling activation and Ang-1-induced angiogenesis. We identified that Tie-2 was modified by advanced glycation end products (AGEs) in aortae derived from high fat diet (HFD)-fed mice and in methylglyoxal (MGO)-treated human umbilical vein endothelial cells (HUVECs). MGO-induced Tie-2 glycation significantly inhibited Ang-1-evoked Tie-2 and Akt phosphorylation and Ang-1-regulated endothelial cell migration and tube formation, whereas the blockade of AGE formation by aminoguanidine remarkably rescued Ang-1 signaling activation and Ang-1-induced angiogenesis in vitro. Furthermore, MGO treatment markedly increased AGE cross-linking of Tie-2 in cultured aortae ex vivo and MGO-induced Tie-2 glycation also significantly decreased Ang-1-induced vessel outgrow from aortic rings. Collectively, these data suggest that Tie-2 may be modified by AGEs in diabetes mellitus and that Tie-2 glycation inhibits Ang-1 signaling activation and Ang-1-induced angiogenesis. This may provide a novel mechanism for Ang-1/Tie-2 signal dysfunction and angiogenesis failure in diabetic ischaemic diseases.

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In situ transplantation of adipose-derived stem cells via photoactivation improves glucose metabolism in obese mice

Cited by 9 publications

References 30 publications

Photomodulation alleviates cellular senescence of aging adipose-derived stem cells

Photomodulation alleviates cellular senescence of aging adipose-derived stem cells

Translating MSC Therapy in the Age of Obesity

Glycation of Tie-2 Inhibits Angiopoietin-1 Signaling Activation and Angiopoietin-1-Induced Angiogenesis

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