IL‐7 enhances the differentiation of adipose‐derived stem cells toward lymphatic endothelial cells through AKT signaling

Sun, Yuan; Lu, Bolun; Deng, Jinhai; Jiang, Zhaohua; Cao, Weigang; Dai, Tingting; Li, Shengli

doi:10.1002/cbin.11093

Cited by 14 publications

(14 citation statements)

References 30 publications

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“…Endothelialization is a fundamental target for researchers and clinicians involved in vascular and valvular replacements ( 29 , 30 ). Varied modalities to differentiate and to promote ADSCs commitment toward ECs were described, including genomic manipulation ( 31 ), immune modulation ( 32 ), induced hypoxia ( 33 ), and specific growth factors ( 34 , 35 ). Comparative studies of differentiation of ADSCs toward ECs lineage revealed improved results when combinations of ECGS and shear were used ( 36 , 37 ) pointing to the importance of recreating the in vivo conditions.…”

Section: Discussionmentioning

confidence: 99%

Preclinical Testing of Living Tissue-Engineered Heart Valves for Pediatric Patients, Challenges and Opportunities

Movileanu

Harpa

Harceaga

et al. 2021

Front. Cardiovasc. Med.

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Introduction: Pediatric patients with cardiac congenital diseases require heart valve implants that can grow with their natural somatic increase in size. Current artificial valves perform poorly in children and cannot grow; thus, living-tissue-engineered valves capable of sustaining matrix homeostasis could overcome the current drawbacks of artificial prostheses and minimize the need for repeat surgeries.Materials and Methods: To prepare living-tissue-engineered valves, we produced completely acellular ovine pulmonary valves by perfusion. We then collected autologous adipose tissue, isolated stem cells, and differentiated them into fibroblasts and separately into endothelial cells. We seeded the fibroblasts in the cusp interstitium and onto the root adventitia and the endothelial cells inside the lumen, conditioned the living valves in dedicated pulmonary heart valve bioreactors, and pursued orthotopic implantation of autologous cell-seeded valves with 6 months follow-up. Unseeded valves served as controls.Results: Perfusion decellularization yielded acellular pulmonary valves that were stable, no degradable in vivo, cell friendly and biocompatible, had excellent hemodynamics, were not immunogenic or inflammatory, non thrombogenic, did not calcify in juvenile sheep, and served as substrates for cell repopulation. Autologous adipose-derived stem cells were easy to isolate and differentiate into fibroblasts and endothelial-like cells. Cell-seeded valves exhibited preserved viability after progressive bioreactor conditioning and functioned well in vivo for 6 months. At explantation, the implants and anastomoses were intact, and the valve root was well integrated into host tissues; valve leaflets were unchanged in size, non fibrotic, supple, and functional. Numerous cells positive for a-smooth muscle cell actin were found mostly in the sinus, base, and the fibrosa of the leaflets, and most surfaces were covered by endothelial cells, indicating a strong potential for repopulation of the scaffold.Conclusions: Tissue-engineered living valves can be generated in vitro using the approach described here. The technology is not trivial and can provide numerous challenges and opportunities, which are discussed in detail in this paper. Overall, we concluded that cell seeding did not negatively affect tissue-engineered heart valve (TEHV) performance as they exhibited as good hemodynamic performance as acellular valves in this model. Further understanding of cell fate after implantation and the timeline of repopulation of acellular scaffolds will help us evaluate the translational potential of this technology.

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Section: Discussionmentioning

confidence: 99%

Preclinical Testing of Living Tissue-Engineered Heart Valves for Pediatric Patients, Challenges and Opportunities

Movileanu

Harpa

Harceaga

et al. 2021

Front. Cardiovasc. Med.

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“…They conducted an in vitro study using human ADSCs (5 × 10 5 cells) cultured by an induced medium with IL-7. They noticed an increase in RNA and protein levels of LEC markers (Prox-1, LYVE-1, podoplanin, and VEGF-3) in the ADSCs cultured with IL-7 and suggested that this cytokine enhances ADSC differentiation into LECs [19].…”

Section: I F F E R E N T I a T I O N P A R A C R I N E S E C R E T I O Nmentioning

confidence: 99%

“…Moreover, tube-like structures were formed by these differentiated ADSCs in the matrix gel [18]. Sun et al [19] aimed to investigate the effect of IL-7 on ADSC differentiation into LECs. They conducted an in vitro study using human ADSCs (5 × 10 5 cells) cultured by an induced medium with IL-7.…”

Section: I F F E R E N T I a T I O N P A R A C R I N E S E C R E T I O Nmentioning

confidence: 99%

Use of adipose-derived stem cells in lymphatic tissue engineering and regeneration

et al. 2021

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The potential to differentiate into different cell lines, added to the easy and cost-effective method of extraction, makes adipose-derived stem cells (ADSCs) an object of interest in lymphedema treatment. Our study’s goal was to conduct a comprehensive systematic review of the use of ADSCs in lymphatic tissue engineering and regeneration. On July 23, 2019, using PubMed/MEDLINE, Cochrane Clinical Answers, Cochrane Central Register of Controlled Trials, and Embase databases, we conducted a systematic review of published literature on the use of ADSCs in lymphatic tissue engineering and regeneration. There were no language or time frame limitations, and the following search strategy was applied: ((Adipose stem cell) OR Adipose-derived stem cell)) AND ((Lymphedema) OR Breast Cancer Lymphedema). Only original research manuscripts were included. Fourteen studies fulfilled the inclusion criteria. Eleven studies were experimental (in vitro or in vivo in animals), and only three were clinical. Publications on the topic demonstrated that ADSCs promote lymphangiogenesis, and its effect could be enhanced by modulation of vascular endothelial growth factor-C, interleukin-7, prospero homeobox protein 1, and transforming growth factor-β1. Pilot clinical studies included 11 patients with breast cancer-related lymphedema, and no significant side effects were present at 12-month follow-up. Literature on the use of ADSCs in lymphatic tissue engineering and regeneration demonstrated promising data. Clinical evidence is still in its infancy, but the scientific community agrees that ADSCs can be useful in regenerative lymphangiogenesis. Data collected in this review indicate that unprecedented advances in lymphedema treatment can be anticipated in the upcoming years.

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“…In addition, ADSCs exhibit paracrine immunomodulatory and trophic effects in their local microenvironment. Emerging in vitro studies have investigated the possible mechanisms and benefit of ADSCs in the treatment of lymphedema, such as their capacity for differentiation into lymphatic endothelial cells (LECs)[ 16 , 17 ] and paracrine secretion of cytokines[ 18 ], chemokines[ 19 ] and exosomes[ 20 ], thereby promoting angiogenesis and modulating the immune response. Takeda et al[ 21 ] reported that, by secreting lymphangiogenic factors, ADSCs promote proliferation, migration, and tube formation of LECs in vitro .…”

Section: Introductionmentioning

confidence: 99%

“…Yen et al[ 23 ] showed that ADSCs promote lymphangiogenesis under stimulation of vascular endothelial growth factor-C (VEGF-C), a key lymphangiogenic factor, or in response to inhibition of TGF-β1; moreover, stimulation of ADSCs with VEGF-C was found to markedly increase cellular proliferation and cellular survival after in vivo implantation and to induce the expression of podoplanin, a lymphangiogenic cell marker. Sun et al[ 19 ] reported that interleukin-7 enhanced the differentiation of ADSCs into LECs via AKT signaling pathways. Most recently, Saijo et al[ 24 ] revealed that paracrine effects of ADSCs promoted lymphangiogenesis in irradiated LECs.…”

Section: Introductionmentioning

confidence: 99%

Application and prospect of adipose stem cell transplantation in treating lymphedema

Li¹,

Yang²,

Li³

et al. 2020

WJSC

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BACKGROUND Lymphedema is a chronic, debilitating and incurable disease that affects 0.13%-2% of the global population. Emerging evidence indicates that adipose-derived stem cells (ADSCs) might serve as suitable seed cells for lymphatic tissue engineering and lymphedema therapy. AIM To summarize applications of ADSCs for treating lymphedema in both animal studies and clinical trials. METHODS A systematic search was performed on four databases – PubMed, Clinicaltrials.gov, the evidence-based Cochrane Library, and OVID – using the following search string: (“lymphedema” or “lymphoedema” or “lymphangiogenesis”) and (“adipose-derived stem cells” or “adipose-derived stromal cells” or “adipose-derived regenerative cells”). A manual search was performed by skimming the references of relevant studies. Animal studies and clinical trials using adipose-derived cells for the treatment of any kind of lymphedema were included. RESULTS A total of eight research articles published before November 2019 were included for this analysis. Five articles focused on animal studies and another three focused on clinical trials. ADSC transplantation therapy was demonstrated to be effective against lymphedema in all studies. The animal studies found that coadministration of ADSCs and controlled-release vascular endothelial growth factor-C or platelet-rich plasma could improve the effectiveness of ADSC therapy. Three sequential clinical trials were conducted on breast cancer-related lymphedema patients, and all showed favorable results. CONCLUSION ADSC-based therapy is a promising option for treating lymphedema. Large-scale, multicenter randomized controlled trials are needed to develop more effective and durable therapeutic strategies.

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IL‐7 enhances the differentiation of adipose‐derived stem cells toward lymphatic endothelial cells through AKT signaling

Cited by 14 publications

References 30 publications

Preclinical Testing of Living Tissue-Engineered Heart Valves for Pediatric Patients, Challenges and Opportunities

Preclinical Testing of Living Tissue-Engineered Heart Valves for Pediatric Patients, Challenges and Opportunities

Use of adipose-derived stem cells in lymphatic tissue engineering and regeneration

Application and prospect of adipose stem cell transplantation in treating lymphedema

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