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. 2020 Jul;40(5):585-592.
doi: 10.1002/micr.30579. Epub 2020 Mar 31.

Adipose derived mesenchymal stem cells seeded onto a decellularized nerve allograft enhances angiogenesis in a rat sciatic nerve defect model

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Adipose derived mesenchymal stem cells seeded onto a decellularized nerve allograft enhances angiogenesis in a rat sciatic nerve defect model

Femke Mathot et al. Microsurgery. 2020 Jul.

Abstract

Purpose: Adipose derived mesenchymal stem cells (MSCs) are hypothesized to supplement tissues with growth factors essential for regeneration and neovascularization. The purpose of this study was to determine the effect of MSCs with respect to neoangiogenesis when seeded onto a decellularized nerve allograft in a rat sciatic nerve defect model.

Methods: Allograft nerves were harvested from Sprague-Dawley rats and decellularized. MSCs were obtained from Lewis rats. 10 mm sciatic nerve defects in Lewis rats were reconstructed with reversed autograft nerves, decellularized allografts, decellularized allografts seeded with undifferentiated MSC or decellularized allografts seeded with differentiated MSCs. At 16 weeks, the vascular surface area and volume were evaluated.

Results: The vascular surface area in normal nerves (34.9 ± 5.7%), autografts (29.5 ± 8.7%), allografts seeded with differentiated (38.9 ± 7.0%) and undifferentiated MSCs (29.2 ± 3.4%) did not significantly differ from each other. Unseeded allografts (21.2 ± 6.2%) had a significantly lower vascular surface area percentage than normal nonoperated nerves (13.7%, p = .001) and allografts seeded with differentiated MSCs (17.8%, p = .001). Although the vascular surface area was significantly correlated to the vascular volume (r = .416; p = .008), no significant differences were found between groups concerning vascular volumes. The vascularization pattern in allografts seeded with MSCs consisted of an extensive nonaligned network of microvessels with a centripetal pattern, while the vessels in autografts and normal nerves were more longitudinally aligned with longitudinal inosculation patterns.

Conclusions: Neoangiogenesis of decellularized allograft nerves was enhanced by stem cell seeding, in particular by differentiated MSCs. The pattern of vascularization was different between decellularized allograft nerves seeded with MSCs compared to autograft nerves.

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Figures

Figure 1.
Figure 1.
Differentiation of MSCs into Schwann-like cells was confirmed by comparing the expression of Schwann cell markers S100 (A-B-C), GFAP (D-E-F) and NTR p75 (G-H-I) in the differentiated MSCs(B-E-H) to the expression in Schwann cells (C-F-I) and undifferentiated MSCs (A-D-G).
Figure 2.
Figure 2.
The vascular surface area outcomes of autografts, allografts, allografts seeded with undifferentiated MSC and allografts seeded with differentiated MSCs. The unseeded allografts showed a significantly lower mean vascular surface percentage than allografts seeded with differentiated MSCs and normal nerves (both p<0.001). Error bars = standard deviation of the mean undifferentiated MSC = undifferentiated Mesenchymal Stem Cells differentiated MSCs = differentiated Mesenchymal Stem Cells *** = p<0.001
Figure 3.
Figure 3.
Conventional images of the vasculature of a normal nerve (A) autografts (B), allografts (C), allografts seeded with undifferentiated MSC (D) and allografts seeded with differentiated MSCs (E). The nerves were positioned from proximal (left) to distal (right). The ingrowth of vessels seem to occurred from both nerve ends, but from proximal in particular. The structuring of the vessels was clearly less organized in our study groups compared to the control nerve.
Figure 4.
Figure 4.
The vascular volume outcomes of autografts, allografts, allografts seeded with undifferentiated MSC and allografts seeded with differentiated MSCs. None of the differences between the groups was statistically significant. Error bars = standard deviation of the mean uMSC = undifferentiated Mesenchymal Stem Cells dMSCs = differentiated Mesenchymal Stem Cells
Figure 5.
Figure 5.
Snapshots of the obtained micro-CT scans that served for the volume measurements of normal nerves (A) autografts (B), allografts (C), allografts seeded with undifferentiated MSCs (D) and allografts seeded with differentiated MSCs (E). The nerves are positioned from proximal (left) to distal (right). The smallest vessels not detected by the micro-CT due to its effective pixel size.

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References

    1. Zhu Z, Huang Y, Zou X, Zheng C, Liu J, Qiu L, et al. The vascularization pattern of acellular nerve allografts after nerve repair in Sprague-Dawley rats. Neurolog Res 2017;39:1014–1021. - PubMed
    1. Niu X, Liu X, Hu J, Jiang L. [Experimental research on revascularization of chemically extracted acellular allogenous nerve graft]. Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chin J Repar Reconstr Surg 2009;23:235–238. - PubMed
    1. Donzelli R, Capone C, Sgulo FG, Mariniello G, Maiuri F. Vascularized nerve grafts: an experimental study. Neurolog Res 2016;38:669–677. - PubMed
    1. Wynn TA, Vannella KM. Macrophages in Tissue Repair, Regeneration, and Fibrosis. Immunity 2016;44:450–462. - PMC - PubMed
    1. Ferretti A, Boschi E, Stefani A, Spiga S, Romanelli M, Lemmi M, et al. Angiogenesis and nerve regeneration in a model of human skin equivalent transplant. Life Sci 2003;73:1985–1994. - PubMed