Early Macrophage Infiltration Improves Fat Graft Survival by Inducing Angiogenesis and Hematopoietic Stem Cell Recruitment

Cai, Junrong; Feng, Jiaxuan; Liu, Kaiyang; Zhou, Shaolong; Lu, Feng

doi:10.1097/prs.0000000000004028

Cited by 79 publications

(87 citation statements)

References 39 publications

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“…They are heterogenous cells which can influence the microenvironment through their polarization into different phenotypes (Brown, Sicari & Badylak, 2014). Over the last few years, the importance of Mφs in stem cell survival and tissue repair has been recognized (Cai et al, 2018). Since Mφs can switch their phenotypes during the process of tissue regeneration (Novak & Koh, 2013), it's essential to explore the regulating effect of different phenotypes of Mφs on MSCs.…”

Section: Discussionmentioning

confidence: 99%

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Exosomes derived from M0, M1 and M2 macrophages exert distinct influences on the proliferation and differentiation of mesenchymal stem cells

Xia

et al. 2020

PeerJ

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Background Different phenotypes of macrophages (M0, M1 and M2 Mφs) have been demonstrated to play distinct roles in regulating mesenchymal stem cells in various in vitro and in vivo systems. Our previous study also found that cell-conditioned medium (CM) derived from M1 Mφs supported the proliferation and adipogenic differentiation of bone marrow mesenchymal stem cells (BMMSCs), whereas CM derived from either M0 or M2 Mφs showed an enhanced effect on cell osteogenic differentiation. However, the underlying mechanism remains incompletely elucidated. Exosomes, as key components of Mφ-derived CM, have received increasing attention. Therefore, it is possible that exosomes may modulate the effect of Mφ-derived CM on the property of BMMSCs. This hypothesis was tested in the present study. Methods In this study, RAW264.7 cells were induced toward M1 or M2 polarization with different cytokines, and exosomes were isolated from the unpolarized (M0) and polarized (M1 and M2) Mφs. Mouse BMMSCs were then cultured with normal complete medium or inductive medium supplemented with M0-Exos, M1-Exos or M2-Exos. Finally, the proliferation ability and the osteogenic, adipogenic and chondrogenic differentiation capacity of the BMMSCs were measured and analyzed. Results We found that only the medium containing M1-Exos, rather than M0-Exos or M2-Exos, supported cell proliferation and osteogenic and adipogenic differentiation. This was inconsistent with CM-based incubation. In addition, all three types of exosomes had a suppressive effect on chondrogenic differentiation. Conclusion Although our data demonstrated that exosomes and CM derived from the same phenotype of Mφs didn’t exert exactly the same cellular influences on the cocultured stem cells, it still confirmed the hypothesis that exosomes are key regulators during the modulation effect of Mφ-derived CM on BMMSC property.

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Section: Discussionmentioning

confidence: 99%

“…Considerable efforts have been made to improve the regenerative efficiency of MSCs in vivo. Currently, the significance of macrophages (Mφs) in the recruitment and modulation of MSCs is well recognized (Zhang et al, 2017a;Ma et al, 2018;Cai et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Exosomes derived from M0, M1 and M2 macrophages exert distinct influences on the proliferation and differentiation of mesenchymal stem cells

Xia

et al. 2020

PeerJ

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“…In the regeneration zone, new small preadipocytes (<20 μm) appear around dead adipocytes within 1 to 2 weeks post transplantation 19 . Fat graft angiogenesis and regeneration begin 1 week after fat transplantation and, peaks at 4 weeks 20,21 . The Two steps group was injected with PRP into the interior of the grafts on the first week (capillaries and preadipocytes begin to regenerate) and second week (the growth rate of capillaries and preadipocytes gradually reached the peak after transplantation).…”

Section: Discussionmentioning

confidence: 99%

“…Macrophages have been shown to be one of an inflammatory cell that predominantly exists in the transplanted micro-environment 21,22 . By week 1, most of the macrophages were M1 polarized, indicating a "inflammatory phase" during which dead cells were cleared.…”

Section: Discussionmentioning

confidence: 99%

“…From week 2 to week 4 and after transplantation, M2 macrophages slowly became dominant, indicating the beginning of the "regeneration phase" 22 . However, the regeneration of fat sometimes halted 8 weeks after transplantation, for the reason that large oil droplets formed by necrotic adipocytes hampered cell proliferations 21,22 . Our results showed that, 14 weeks after transplantation, more M2 macrophages gathered around the oil droplets in the Two steps group (Fig.…”

Section: Discussionmentioning

confidence: 99%

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Delayed two steps PRP injection strategy for the improvement of fat graft survival with superior angiogenesis

Mou

Peng

et al. 2020

Sci Rep

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platelet-rich plasma (pRp) has been widely used to improve the fat retention rate in autologous fat transplantation since it possesses a good angiogenesis capability in vivo. However, due to the short halflife of growth factors released from PRP and its uneven distribution in injected fat tissue, the strategy of pRp in fat transplantation needs further improvement. Since the capillaries started to grow into fat grafts in 1 week and vascular growth peaks in the second week after transplantation, we hypothesized that delayed two-steps PRP injection into the interior of grafts, accompanied with the extent of neovascularization might theoretically promote microvessel growth inside transplanted adipose tissue. 24 nude mice were divided into three groups: Blank group (0.35 mL fat mixed with 0.15 mL saline, n = 8), Single step group (0.35 mL fat mixed with 0.15 mLPRP, N = 8), and Two steps group (0.35 mL fat (day 0) + 0.075 mL PRP (day 7) + 0.075 mL PRP (day 14), N = 8). At 6 and 14 weeks post-transplantation, grafts were dissected, weighted, and assessed for histology, angiogenesis, fat regeneration and inflammation level. The weight and volume of the fat samples revealed no statistical difference among the three groups at 6 weeks after fat transplantation. The weight and volume of the Two steps group fat samples showed significantly higher compared to that in Blank and Single step groups at 14 weeks after fat transplantation (weight: 137.25 ± 5.60 mg versus 87.5 ± 3.90 mg,106.75 ± 2.94 mg, respectively; volume: 0.13 ± 0.01 mL versus 0.08 ± 0.01 mL, 0.09 ± 0.01 mL, respectively). Histological assessments indicated that delayed two-steps pRp injection strategy helps to improve adipose tissue content and reduce the composition of fibrous connective tissue at 14 weeks after fat transplantation. At 6 weeks and 14 weeks after transplantation, CD31 immunofluorescence indicated that delayed two-steps PRP injection strategy helps to improve angiogenesis and significantly higher compared to that in Blank and Single step groups (6 weeks: 28.75 ± 4.54 versus 10.50 ± 2.06, 21.75 ± 1.85; 14 weeks: 21.75 ± 2.86 versus 9.87 ± 2.08, 11.75 ± 1.47, respectively). Preadipocyte count indicated delayed two-steps PRP injection strategy might promote fat regeneration and significantly higher compared to that in Blank and Single step groups at 14 weeks (129.75 ± 6.57 versus 13.50 ± 3.50, 17.12 ± 6.23, respectively). In this study, we demonstrated that the novel delayed two-steps PRP injection strategy remarkably enhanced the long-term fat retention rate and improved the neovascularization extent in the interior of the fat graft. Platelet-rich plasma, Delayed two-steps injection, Angiogenesis, Fat transplantation Autologous fat transplantation has become popular for its well convenience and biocompatibility in the application of soft-tissue augmentation 1. However, the fat grafting retention rate is still less than ideal 2,3. The results of retention rate are varied (approximately 20% to 75%) 2,3. Many studies have investigated that the adipos...

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Clinical Applicability of Visible Light‐Mediated Cross‐linking for Structural Soft Tissue Reconstruction

Major,

Longoni,

Simcock

et al. 2023

Advanced Science

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Visible light‐mediated cross‐linking has utility for enhancing the structural capacity and shape fidelity of laboratory‐based polymers. With increased light penetration and cross‐linking speed, there is opportunity to extend future applications into clinical spheres. This study evaluated the utility of a ruthenium/sodium persulfate photocross‐linking system for increasing structural control in heterogeneous living tissues as an example, focusing on unmodified patient‐derived lipoaspirate for soft tissue reconstruction. Freshly‐isolated tissue is photocross‐linked, then the molar abundance of dityrosine bonds is measured using liquid chromatography tandem mass spectrometry and the resulting structural integrity assessed. The cell function and tissue survival of photocross‐linked grafts is evaluated ex vivo and in vivo, with tissue integration and vascularization assessed using histology and microcomputed tomography. The photocross‐linking strategy is tailorable, allowing progressive increases in the structural fidelity of lipoaspirate, as measured by a stepwise reduction in fiber diameter, increased graft porosity and reduced variation in graft resorption. There is an increase in dityrosine bond formation with increasing photoinitiator concentration, and tissue homeostasis is achieved ex vivo, with vascular cell infiltration and vessel formation in vivo. These data demonstrate the capability and applicability of photocrosslinking strategies for improving structural control in clinically‐relevant settings, potentially achieving more desirable patient outcomes using minimal manipulation in surgical procedures.

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Early Macrophage Infiltration Improves Fat Graft Survival by Inducing Angiogenesis and Hematopoietic Stem Cell Recruitment

Cited by 79 publications

References 39 publications

Exosomes derived from M0, M1 and M2 macrophages exert distinct influences on the proliferation and differentiation of mesenchymal stem cells

Exosomes derived from M0, M1 and M2 macrophages exert distinct influences on the proliferation and differentiation of mesenchymal stem cells

Delayed two steps PRP injection strategy for the improvement of fat graft survival with superior angiogenesis

Clinical Applicability of Visible Light‐Mediated Cross‐linking for Structural Soft Tissue Reconstruction

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