Botulinum toxin A and lidocaine have an impact on adipose-derived stem cells, fibroblasts, and mature adipocytes in vitro

Gugerell, Alfred; Schmid, Melanie; Nickl, Stefanie; Kamolz, Lars‐Peter; Keck, Maike

doi:10.1016/j.bjps.2014.05.029

Cited by 22 publications

(23 citation statements)

References 30 publications

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“…In that course, we still tested BoNT on normal human fibroblasts and could show that there is no negative influence on these cells. 10 Nevertheless, a comparison between normal human fibroblasts and scar-derived fibroblasts would be interesting.…”

Section: Discussionmentioning

confidence: 99%

“…As already discussed in a previous study, 10 a wide range of concentrations of BoNT is used in the clinical settings. In the literature, concentrations between 1 and 10 IU/mL were used 11,24–26 ; according to the package inserts, a dose of 5 IU per injection for overactive bladder, 1.25 to 2.5 units per injection for blepharospasm or strabismus (Botox), 27 and 4 IU per intramuscular injection (Botox Cosmetic, Allergan Inc., Irvine, Calif.) 28 are recommended.…”

Section: Discussionmentioning

confidence: 99%

“…10 Botulinum toxin was shown to have no negative effect on adipose-derived stem cells, mature adipocytes, or fibroblasts. BoNT was also used as an adjuvant in autologous fat transfer in vivo where a higher fat graft survival could be achieved.…”

mentioning

confidence: 99%

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Botulinum Toxin A: Dose-dependent Effect on Reepithelialization and Angiogenesis

Gugerell

Schmid

Buchberger

et al. 2016

Plastic and Reconstructive Surgery - Global Open

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Background:Botulinum (neuro)toxin A (BoNT) is widely used in the field of plastic and reconstructive surgery. Among treatment of pain, hyperhidrosis, or aesthetic purposes, it is also used to enhance wound healing and prevent excessive scar formation. Some clinical data already exist, but only little is known on a cellular level. The aim of this study was to evaluate the effect of BoNT on cells essential for wound healing in vitro. Therefore, primary human keratinocytes and endothelial cells were treated with different concentrations of BoNT and tested on proliferation, migration, and angiogenic behavior.Methods:BoNT was exposed to human keratinocytes and endothelial cells in a low (1 IU/mL), medium (10 IU/mL), and high (20 IU/mL) concentrations in cell culture. Proliferation and migration of the 2 cell types were observed and also the angiogenic potential of endothelial cells in vitro.Results:BoNT 20 IU/mL negatively influenced proliferation and migration of keratinocytes but not those of endothelial cells. Angiogenesis in vitro was less effective with the highest BoNT concentrations tested. Low concentrations of BoNT supported sprouting of endothelial cells.Conclusions:High concentrations of botulinum toxin interfered with wound closure as keratinocytes’ proliferation and migration were deteriorated. Furthermore, BoNT concentrations of 20 IU/mL constrain in vitro vessel formation but do not influence proliferation or migration of endothelial cells.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Botulinum Toxin A: Dose-dependent Effect on Reepithelialization and Angiogenesis

Gugerell

Schmid

Buchberger

et al. 2016

Plastic and Reconstructive Surgery - Global Open

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“…BoNTA has been proven to have no negative effect on ASCs after adipose tissue engraftment (37). In the study by Sunaga et al , after grafting, the proliferation of ASCs increased on day 3.…”

Section: Discussionmentioning

confidence: 99%

Botulinum toxin A improves adipose tissue engraftment by promoting cell proliferation, adipogenesis and angiogenesis

Tang

Chen

Wang

et al. 2017

International Journal of Molecular Medicine

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Adipose tissue engraftment has become a well-established therapy in plastic and reconstructive surgery used to restore age-related or injury-related soft tissue loss. However, the unpredictable absorption rates limit its further application. Some clinicians have noted that more optimal aesthetic results are achieved when botulinum toxin A (BoNTA) is applied prior to adipose tissue grafting. In the present study, we transplanted allogeneic adipose tissue treated with or without BoNTA in SD rats in vivo. We subsequently evaluated the survival rate (weight, volume, apoptosis and cellular integrity) and revascularization of the adipose tissue. The results revealed that BoNTA improved the long-term weight and volume retention of the graft, and preserved cellular integrity. BoNTA significantly increased the expression levels of CD31 and vascular endothelial growth factor (VEGF), suggesting enhanced vasodilation and endothelial cell proliferation. In vitro, adipose-derived stem cells (ASCs) were isolated, identified and induced to proliferate and differentiate with or without BoNTA. Furthermore, to evaluate the proliferative, adipogenic and angiogenic ability of the ASCs, CCK-8 assay and Oil Red O staining were conducted. Gene and protein expression levels were analyzed by RT-qPCR and western blot analysis. The results revealed that 8×10−2 U/ml BoNTA as the optimal dose increased ASC proliferation and adipogenic differentiation capacity, as well as the expression level of the key cytokine of angiogenesis. On the whole, our findings indicate that BoNTA improves adipose tissue engraftment and promotes ASC regeneration, which could benefit future clinical applications.

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“…Like other anesthetics in its class, lidocaine is known to inhibit sodium voltage‐dependent channels in nerve cells, thus preventing nerve signal conduction and thereby reducing pain. Some previous studies have shown cytotoxic effects of local anesthetic agents on MSCs . Previous work performed by Breu et al and Dregalla et al examining the effects of local anesthetics on bone marrow MSCs demonstrated that amide‐type local anesthetics had detrimental cytotoxic effects on MSC monolayer cultures in a concentration‐ and time‐specific manner .…”

Section: Introductionmentioning

confidence: 96%

Effect of Lidocaine on Viability and Gene Expression of Human Adipose–derived Mesenchymal Stem Cells: An in vitro Study

Nie

Kubrova

et al. 2019

PM&R

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Objective To assess the biologic effects of lidocaine on the viability, proliferation, and function of human adipose tissue–derived mesenchymal stromal/stem cells (MSCs) in vitro. Methods Adipose‐derived MSCs from three donors were exposed to lidocaine at various dilutions (2 mg/mL to 8 mg/mL) and exposure times (0.5 to 4 hours). Cell number and viability, mitochondrial activity, and real‐time reverse‐transcriptase quantitative polymerase chain reaction (RT‐qPCR) were analyzed at 0 (immediate effects) or 24 and 48 hours (recovery effects) after treatment with lidocaine. Results Trypan blue staining showed that increasing concentrations of lidocaine decreased the number of observable viable cells. 3‐[4,5,dimethylthiazol‐2‐yl]‐5‐[3‐carboxymethoxy‐phenyl]‐2‐[4‐sulfophenyl]‐2H‐tetrazolium (MTS) assays revealed a concentration‐ and time‐ dependent decline of mitochondrial activity and proliferative ability. Gene expression analysis by RT‐qPCR revealed that adipose‐derived MSCs exposed to lidocaine express robust levels of stress response/cytoprotective genes. However, higher concentrations of lidocaine caused a significant downregulation of these genes. No significant differences were observed in expression of extracellular matrix (ECM) markers COL1A1 and DCN except for COL3A1 (P < .05). Levels of messenger RNA (mRNA) for proliferation markers (CCNB2, HIST2H4A, P < .001) and MKI67 (P < .001) increased at 24 and 48 hours. Expression levels of several transcription factors— including SP1, PRRX1, and ATF1—were modulated in the same manner. MSC surface markers CD44 and CD105 demonstrated decreased expression immediately after treatment, but at 24 and 48 hours postexposure, the MSC markers showed no significant difference among groups. Conclusion Lidocaine is toxic to MSCs in a dose‐ and time‐ dependent manner. MSC exposure to high (4‐8 mg/mL) concentrations of lidocaine for prolonged periods can affect their biologic functions. Although the exposure time in vivo is short, it is essential to choose safe concentrations when applying lidocaine along with MSCs to avoid compromising the viability and potency of the stem cell therapy.

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Botulinum toxin A and lidocaine have an impact on adipose-derived stem cells, fibroblasts, and mature adipocytes in vitro

Cited by 22 publications

References 30 publications

Botulinum Toxin A: Dose-dependent Effect on Reepithelialization and Angiogenesis

Botulinum Toxin A: Dose-dependent Effect on Reepithelialization and Angiogenesis

Botulinum toxin A improves adipose tissue engraftment by promoting cell proliferation, adipogenesis and angiogenesis

Effect of Lidocaine on Viability and Gene Expression of Human Adipose–derived Mesenchymal Stem Cells: An in vitro Study

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