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Effects of miR126 Expressing Adipose-Derived Stem Cells on Fat Graft Survival and Angiogenesis

  • Original Article
  • Basic Science/Experimental
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Abstract

Background

Fat transplantation supported by supplementation with ASCs has become a reliable procedure for treating soft tissue defects. However, the unpredictable survival rates for grafted fat remains a challenge with post-transplantation ischemia causing tissue loss. MiR126, which regulates VEGF signaling, is an endothelial cell-specific miRNA known to play an essential role in angiogenesis. We hypothesized that increased miR126 expression in grafted ASCs may promote fat survival within an autologous fat transfer model.

Methods

Rat adipose-derived stem cells were isolated, expanded ex vivo for three passages and then transduced with miR126. We used PCR to verify lentiviral transduction and ELISA to confirm VEGF expression. We then mixed autologous fat tissues from our rat model with transduced ASCs, augmented with a nonsense control or miR126 expression vector. These mixtures were used in the fat grafting procedure, completed via subcutaneous injection at three paravertebral points in each rat. Fat grafts were then harvested on days 4, 7, 14, and 28 post-transplant and evaluated for survival, neovascularization, and protein expression via western blot.

Results

VEGF expression levels in ASCs, Con-ASCs, and miR126-ASCs were not significantly different. However, miR126-ASCs experienced significantly improved survival on days 7, 14, and 28 when compared with the other groups. These ASCs also presented with the greatest capillary density on days 7, 14, and 28 post-transplantation as well as increased p-ERK and p-AKT expression when compared to the other groups.

Conclusion

This data suggests that miR126 augmentation of ASCs may help to enhance the survival and angiogenic capacity of transplanted fat tissues, and that this augmentation was not dependent on VEGF but rather the activation of the ERK/AKT pathway.

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Abbreviations

ASCs:

Adipose-derived stem cells

VEGF:

Vascular endothelial growth factor

IL-10:

Anti-inflammatory cytokine interleukin 10

qRT-PCR:

Quantitative reverse transcriptional-Tim PCR

ELISA:

Enzyme-linked immunosorbent assay

PBS:

Phosphate buffered saline

References

  1. Rubin JP, Marra KG (2011) Soft tissue reconstruction. Methods Mol Biol 702:395–400

    Article  CAS  PubMed  Google Scholar 

  2. Clark N, Sherman R (1993) Soft-tissue reconstruction of the foot and ankle. Orthop Clin North Am 24:489–503

    Article  CAS  PubMed  Google Scholar 

  3. Carpaneda CA, Ribeiro MT (1993) Study of the histologic alterations and viability of the adipose graft in humans. Aesthetic Plast Surg 17:43–47

    Article  CAS  PubMed  Google Scholar 

  4. Coleman SR (2006) Structural fat grafting: more than a permanent filler. Plast Reconstr Surg 118:108S-120S

    Article  CAS  PubMed  Google Scholar 

  5. Herold C, Ueberreiter K, Busche MN et al (2013) Autologous fat transplantation: volumetric tools for estimation of volume survival A systematic review. Aesthetic Plast Surg 37:380–387

    Article  PubMed  Google Scholar 

  6. Ross RJ, Shayan R, Mutimer KL et al (2014) Autologous fat grafting: current state of the art and critical review. Ann Plast Surg 73:352–357

    Article  CAS  PubMed  Google Scholar 

  7. Eto H, Kato H, Suga H et al (2012) The fate of adipocytes after nonvascularized fat grafting: evidence of early death and replacement of adipocytes. Plast Reconstr Surg 129:1081–1092

    Article  CAS  PubMed  Google Scholar 

  8. Gan F, Liu L, Zhou Q et al (2022) Effects of adipose-derived stromal cells and endothelial progenitor cells on adipose transplant survival and angiogenesis. PLoS ONE 17:e261498

    Article  Google Scholar 

  9. Vanderstichele S, Vranckx JJ (2022) Anti-fibrotic effect of adipose-derived stem cells on fibrotic scars. World J Stem Cells 14:200–213

    Article  PubMed  PubMed Central  Google Scholar 

  10. Inui M, Martello G, Piccolo S (2010) MicroRNA control of signal transduction. Nat Rev Mol Cell Biol 11:252–263

    Article  CAS  PubMed  Google Scholar 

  11. Endo-Takahashi Y, Negishi Y, Nakamura A et al (2014) Systemic delivery of miR-126 by miRNA-loaded Bubble liposomes for the treatment of hindlimb ischemia. Sci Rep 4:3883

    Article  PubMed  PubMed Central  Google Scholar 

  12. Shoshani O, Livne E, Armoni M et al (2005) The effect of interleukin-8 on the viability of injected adipose tissue in nude mice. Plast Reconstr Surg 115:853–859

    Article  CAS  PubMed  Google Scholar 

  13. Chajchir A (1996) Fat injection: long-term follow-Up. Aesthetic Plast Surg 20:291–296

    Article  CAS  PubMed  Google Scholar 

  14. Zuk PA, Zhu M, Ashjian P et al (2002) Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell 13:4279–4295

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Yoshimura K, Sato K, Aoi N et al (2008) Cell-assisted lipotransfer for cosmetic breast augmentation: supportive use of adipose-derived stem/stromal cells. Aesthetic Plast Surg 32(48–55):56–57

    Google Scholar 

  16. Gontijo-de-Amorim NF, Charles-de-Sa L, Rigotti G (2017) Mechanical supplementation with the stromal vascular fraction yields improved volume retention in facial lipotransfer: a 1-Year comparative study. Aesthet Surg J 37:975–985

    Article  PubMed  Google Scholar 

  17. Kolle ST, Duscher D, Taudorf M et al (2020) Ex vivo-expanded autologous adipose tissue-derived stromal cells ensure enhanced fat graft retention in breast augmentation: a randomized controlled clinical trial. Stem Cells Transl Med 9:1277–1286

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Gentile P, Sterodimas A, Calabrese C et al (2020) Regenerative application of stromal vascular fraction cells enhanced fat graft maintenance: clinical assessment in face rejuvenation. Expert Opin Biol Ther 20:1503–1513

    Article  PubMed  Google Scholar 

  19. Naderi N, Combellack EJ, Griffin M et al (2017) The regenerative role of adipose-derived stem cells (ADSC) in plastic and reconstructive surgery. Int Wound J 14:112–124

    Article  PubMed  Google Scholar 

  20. Horie H, Hisatome I, Kurata Y et al (2022) alpha1-Adrenergic receptor mediates adipose-derived stem cell sheet-induced protection against chronic heart failure after myocardial infarction in rats. Hypertens Res 45:283–291

    Article  CAS  PubMed  Google Scholar 

  21. Bartynski J, Marion MS, Wang TD (1990) Histopathologic evaluation of adipose autografts in a rabbit ear model. Otolaryngol Head Neck Surg 102(4):314–321

    Article  CAS  PubMed  Google Scholar 

  22. Yamaguchi M, Matsumoto F, Bujo H et al (2005) Revascularization determines volume retention and gene expression by fat grafts in mice. Exp Biol Med (Maywood) 230:742–748

    Article  CAS  PubMed  Google Scholar 

  23. Lei M, Liu SQ, Peng H et al (2008) Effect of rhVEGF gene transfection on survival of grafts after autologous free granular fat transplantation in rats. Chin J Traumatol 11:49–53

    Article  CAS  PubMed  Google Scholar 

  24. Nishimura T, Hashimoto H, Nakanishi I et al (2000) Microvascular angiogenesis and apoptosis in the survival of free fat grafts. Laryngoscope 110:1333–1338

    Article  CAS  PubMed  Google Scholar 

  25. Lu F, Li J, Gao J et al (2009) Improvement of the survival of human autologous fat transplantation by using VEGF-transfected adipose-derived stem cells. Plast Reconstr Surg 124:1437–1446

    Article  CAS  PubMed  Google Scholar 

  26. Wang S, Aurora AB, Johnson BA et al (2008) The endothelial-specific microRNA miR-126 governs vascular integrity and angiogenesis. Dev Cell 15:261–271

    Article  PubMed  PubMed Central  Google Scholar 

  27. van Solingen C, Seghers L, Bijkerk R et al (2009) Antagomir-mediated silencing of endothelial cell specific microRNA-126 impairs ischemia-induced angiogenesis. J Cell Mol Med 13:1577–1585

    Article  PubMed  Google Scholar 

  28. Tauber Z, Cizkova K, Janikova M et al (2019) Serum C-peptide level correlates with the course of muscle tissue healing in the rabbit model of critical limb ischemia. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 163:132–140

    Article  PubMed  Google Scholar 

  29. Qiu C, Xie Q, Zhang D et al (2014) GM-CSF induces cyclin D1 expression and proliferation of endothelial progenitor cells via PI3K and MAPK signaling. Cell Physiol Biochem 33:784–795

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by the East Hospital affiliated with Tongji University introduced a talent research startup fund (Grant Number DFRC2019008), and the featured clinical discipline project of Shanghai Pudong (Grant Number PWYts2021-07).

Funding

This work was supported by the East Hospital affiliated with Tongji University introduced a talent research startup fund (Grant Number DFRC2019008), and the featured clinical discipline project of Shanghai Pudong (Grant Number PWYts2021-07).

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Author notes

  1. Xiang Jie, Hao Hu and Bing Nie contributed equally to this work.

Authors and Affiliations

  1. Department of Plastic and Reconstructive Surgery, Second Affiliated Hospital of Naval Medical University, 415 Fengyang Road, Shanghai, 200003, China

    Xiang Jie, Bing Nie, Lie Zhu, Hua Jiang & Antang Liu

  2. Department of Plastic Surgery, School of Medicine, Shanghai East Hospital, Tongji University, 150 Jimo Road, Shanghai, 200120, China

    Hao Hu & Hua Jiang

  3. Department of Plastic and Reconstructive Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 85/86 Wujin Road, Shanghai, 200080, China

    Antang Liu

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  1. Xiang Jie
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  4. Lie Zhu
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Contributions

XJ, HH, and BN performed the experiment. AL, LZ, and HJ designed the experimental technique. XJ and BN analyzed the data. XJ and HH wrote the paper.

Corresponding authors

Correspondence to Lie Zhu, Hua Jiang or Antang Liu.

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Jie, X., Hu, H., Nie, B. et al. Effects of miR126 Expressing Adipose-Derived Stem Cells on Fat Graft Survival and Angiogenesis. Aesth Plast Surg 47, 825–832 (2023). https://doi.org/10.1007/s00266-022-03077-1

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