Therapeutic vascularization in regenerative medicine

Gianni‐Barrera, Roberto; Maggio, Nunzia Di; Melly, Ludovic; Burger, Maximilian G.; Mujagić, Edin; Gürke, Lorenz; Schaefer, Dirk J.; Banfi, Andrea

doi:10.1002/sctm.19-0319

Cited by 67 publications

(55 citation statements)

References 95 publications

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“…As was the case with HGF, VEGF was observed to increase the least significantly after 7 day cryotherapy. This growth factor improves skeletal muscle repair through modulation of angiogenesis, however, recent studies concerning therapeutic vascularization have demonstrated that the mechanism is regulated by PDGF BB [46]. Therefore, we conclude that a decrease in the synthesis and secretion of HGF, IGF-1, PDGF BB , and VEGF can delay muscle regeneration in athletes.…”

Section: Discussionmentioning

confidence: 66%

Multiple Cryotherapy Attenuates Oxi-Inflammatory Response Following Skeletal Muscle Injury

Zembroń-Łacny

Morawin

Wawrzyniak-Gramacka

et al. 2020

IJERPH

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The oxi-inflammatory response is part of the natural process mobilizing leukocytes and satellite cells that contribute to clearance and regeneration of damaged muscle tissue. In sports medicine, a number of post-injury recovery strategies, such as whole-body cryotherapy (WBC), are used to improve skeletal muscle regeneration often without scientific evidence of their benefits. The study was designed to assess the impact of WBC on circulating mediators of skeletal muscle regeneration. Twenty elite athletes were randomized to WBC group (3-min exposure to −120 °C, twice a day for 7 days) and control group. Blood samples were collected before the first WBC session and 1 day after the last cryotherapy exposure. WBC did not affect the indirect markers of muscle damage but significantly reduced the generation of reactive oxygen and nitrogen species (H2O2 and NO) as well as the concentrations of serum interleukin 1β (IL-1β) and C-reactive protein (CRP). The changes in circulating growth factors, hepatocyte growth factor (HGF), insulin-like growth factor (IGF-1), platelet-derived growth factor (PDGFBB), vascular endothelial growth factor (VEGF), and brain-derived neurotrophic factor (BDNF), were also reduced by WBC exposure. The study demonstrated that WBC attenuates the cascade of injury–repair–regeneration of skeletal muscles whereby it may delay skeletal muscle regeneration.

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Section: Discussionmentioning

confidence: 66%

Multiple Cryotherapy Attenuates Oxi-Inflammatory Response Following Skeletal Muscle Injury

Zembroń-Łacny

Morawin

Wawrzyniak-Gramacka

et al. 2020

IJERPH

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“…This likely reflects the basic principle that is easier to bring down a house than to build one new. Understanding basic pro-angiogenesis principles will be crucial to achieve a clinical benefit for patients suffering from cardiovascular ischemic disease such as coronary artery disease or peripheral artery disease [45][46][47][48]. It will also be relevant for tissue regeneration, since poor blood vessel growth is one commonality in all types of chronic wounds leading to poor wound bed perfusion and granulation tissue formation [49].…”

Section: Angiogenesis Translational Researchmentioning

confidence: 99%

Endothelial sprouting, proliferation, or senescence: tipping the balance from physiology to pathology

Mühleder

Fernández-Chacón

García-González

et al. 2020

Cell. Mol. Life Sci.

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Therapeutic modulation of vascular cell proliferation and migration is essential for the effective inhibition of angiogenesis in cancer or its induction in cardiovascular disease. The general view is that an increase in vascular growth factor levels or mitogenic stimulation is beneficial for angiogenesis, since it leads to an increase in both endothelial proliferation and sprouting. However, several recent studies showed that an increase in mitogenic stimuli can also lead to the arrest of angiogenesis. This is due to the existence of intrinsic signaling feedback loops and cell cycle checkpoints that work in synchrony to maintain a balance between endothelial proliferation and sprouting. This balance is tightly and effectively regulated during tissue growth and is often deregulated or impaired in disease. Most therapeutic strategies used so far to promote vascular growth simply increase mitogenic stimuli, without taking into account its deleterious effects on this balance and on vascular cells. Here, we review the main findings on the mechanisms controlling physiological vascular sprouting, proliferation, and senescence and how those mechanisms are often deregulated in acquired or congenital cardiovascular disease leading to a diverse range of pathologies. We also discuss alternative approaches to increase the effectiveness of pro-angiogenic therapies in cardiovascular regenerative medicine.

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“…Upon reaching the first confluence, rBMSC were FACS purified in order to remove non-transduced cells and to yield pure CD4-positive populations ( Figure 1C), which were replated for in vitro cell expansion. Removal of non-transduced cells was done to ensure a homogeneous distribution of the signal throughout the constructs, because VEGF binds tightly to extracellular matrix and therefore remains highly localized in the microenvironment around each producing cell in vivo and does not diffuse through tissue (Ozawa et al, 2004;Gianni-Barrera et al, 2020). Production of VEGF protein by VEGF-expressing rBMSC was confirmed by ELISA (609.5 ± 284.6 ng/10 6 cells/day of rabbit VEGF), whereas naïve and CD4-rBMSC secreted background amounts (23.5 ± 22.9 and 24.2 ± 25.9 ng/10 6 cells/day, respectively).…”

Section: Generation Of Facs-sortable Vegf-expressing Rbmscmentioning

confidence: 99%

“…Vascular Endothelial Growth Factor (VEGF) is the master regulator of blood vessel growth and the key molecular target of strategies to promote vascular network expansion in regenerative medicine (Gianni-Barrera et al, 2020). Here, we test the hypothesis that increased angiogenic stimulation from within the core of bone constructs by VEGF can significantly accelerate early vascular in-growth, improve graft perfusion and therefore ensure cell viability deeper in the construct.…”

Section: Introductionmentioning

confidence: 99%

VEGF Over-Expression by Engineered BMSC Accelerates Functional Perfusion, Improving Tissue Density and In-Growth in Clinical-Size Osteogenic Grafts

Largo

Burger

Harschnitz

et al. 2020

Front. Bioeng. Biotechnol.

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The first choice for reconstruction of clinical-size bone defects consists of autologous bone flaps, which often lack the required mechanical strength and cause significant donor-site morbidity. We have previously developed biological substitutes in a rabbit model by combining bone tissue engineering and flap pre-fabrication. However, spontaneous vascularization was insufficient to ensure progenitor survival in the core of the constructs. Here, we hypothesized that increased angiogenic stimulation within constructs by exogenous VEGF can significantly accelerate early vascularization and tissue in-growth. Bone marrow stromal cells from NZW rabbits (rBMSC) were transduced with a retroviral vector to express rabbit VEGF linked to a truncated version of rabbit CD4 as a cell-surface marker. Autologous cells were seeded in clinical-size 5.5 cm 3 HA scaffolds wrapped in a panniculus carnosus flap to provide an ample vascular supply, and implanted ectopically. Constructs seeded with VEGFexpressing rBMSC showed significantly increased progenitor survivival, depth of tissue ingrowth and amount of mineralized tissue. Contrast-enhanced MRI after 1 week in vivo showed significantly improved tissue perfusion in the inner layer of the grafts compared to controls. Interestingly, grafts containing VEGF-expressing rBMSC displayed a hierarchically organized functional vascular tree, composed of dense capillary networks in the inner layers connected to large-caliber feeding vessels entering the constructs at the periphery. These data constitute proof of principle that providing sustained VEGF signaling, independently of cells experiencing hypoxia, is effective to drive rapid vascularization and increase early perfusion in clinical-size osteogenic grafts, leading to improved tissue formation deeper in the constructs.

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Therapeutic vascularization in regenerative medicine

Cited by 67 publications

References 95 publications

Multiple Cryotherapy Attenuates Oxi-Inflammatory Response Following Skeletal Muscle Injury

Multiple Cryotherapy Attenuates Oxi-Inflammatory Response Following Skeletal Muscle Injury

Endothelial sprouting, proliferation, or senescence: tipping the balance from physiology to pathology

VEGF Over-Expression by Engineered BMSC Accelerates Functional Perfusion, Improving Tissue Density and In-Growth in Clinical-Size Osteogenic Grafts

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