scholarly journals Human Mesenchymal Stromal Cell-Derived Exosomes Promote In Vitro Wound Healing by Modulating the Biological Properties of Skin Keratinocytes and Fibroblasts and Stimulating Angiogenesis

2021 ◽  
Vol 22 (12) ◽  
pp. 6239
Author(s):  
Raluca Tutuianu ◽  
Ana-Maria Rosca ◽  
Daniela Madalina Iacomi ◽  
Maya Simionescu ◽  
Irina Titorencu

Bone marrow-derived mesenchymal stromal cells (MSCs) are major players in regenerative therapies for wound healing via their paracrine activity, mediated partially by exosomes. Our purpose was to test if MSC-derived exosomes could accelerate wound healing by enhancing the biological properties of the main cell types involved in the key phases of this process. Thus, the effects of exosomes on (i) macrophage activation, (ii) angiogenesis, (iii) keratinocytes and dermal fibroblasts proliferation and migration, and (iv) the capacity of myofibroblasts to regulate the turnover of the extracellular matrix were evaluated. The results showed that, although exosomes did not exhibit anti-inflammatory properties, they stimulated angiogenesis. Exposure of keratinocytes and dermal (myo)fibroblasts to exosomes enhanced their proliferation and migratory capacity. Additionally, exosomes prevented the upregulation of gene expression for type I and III collagen, α-smooth muscle actin, and MMP2 and 14, and they increased MMP13 expression during the fibroblast–myofibroblast transition. The regenerative properties of exosomes were validated using a wound healing skin organotypic model, which exhibited full re-epithelialization upon exosomes exposure. In summary, these data indicate that exosomes enhance the biological properties of keratinocytes, fibroblasts, and endothelial cells, thus providing a reliable therapeutic tool for skin regeneration.

Molecules ◽  
2018 ◽  
Vol 23 (9) ◽  
pp. 2215 ◽  
Author(s):  
Da Kim ◽  
Ji Jang ◽  
Song Jang ◽  
Jungsun Lee

The neuropeptide substance P (SP) is known to stimulate wound healing by regulating the production of relevant cytokines as well as cell proliferation and migration. However, the therapeutic application of SP is limited by its low stability under biological conditions and oxidation during purification, formulation, and storage. To address this problem, we developed a novel formulation of SP as an SP gel, and investigated its wound healing activity both in vitro and in vivo. SP in SP gel was stable at various temperatures for up to 4 weeks. In vitro, SP gel exhibited more potential as a candidate wound-healing agent than SP alone, as evidenced by the observed increases in the proliferation and migration of human epidermal keratinocytes and human dermal fibroblasts. In vivo experiments showed that SP gel treatment enhanced the healing of full-thickness wounds in mice as compared to SP alone. These results demonstrate the benefits of SP gel as a promising topical agent for wound treatment.


2007 ◽  
Vol 342-343 ◽  
pp. 401-404 ◽  
Author(s):  
Yeon I Woo ◽  
Hyun Joo Son ◽  
Hye Ryeon Lim ◽  
Mi Hee Lee ◽  
Hyun Sook Baek ◽  
...  

Glucans have been reported to stimulate immunity and to promote wound healing. Adult human dermal fibroblast (aHDF) cultured in serum free (serum-starvation). Proliferation of aHDF was measured at various concentrations of β-glucan by MTT assay, and migration was observed for 36h on microscope. The result of fibroblast bioassay, β-glucan had positive influence. In this study, the direct effects of β-glucan on proliferation and migration of human dermal fibroblasts were examined in vitro. That means β-D-glucan has the effect to enhance proliferation and aHDF migration speed, and has the potential as a wound healing agent.


Author(s):  
Byungcheol Lee ◽  
Jisun Song ◽  
Arim Lee ◽  
Daeho Cho ◽  
Tae Sung Kim

Visfatin, a member of the adipokine family, plays an important role in many metabolic and stress responses. The mechanisms underlying the direct therapeutic effects of visfatin on wound healing have not been reported yet. In this study, we examined the effects of visfatin on wound healing in vitro and in vivo. Visfatin enhanced the proliferation and migration of human dermal fibroblasts (HDFs) and keratinocytes, and significantly increased the expression of wound healing-related vascular endothelial growth factor (VEGF) in vitro and in vivo. Treatment of HDFs with visfatin induced activation of both extracellular signal-regulated kinases 1 and 2 (ERK1/2) and c-Jun N-terminal kinases 1 and 2 (JNK1/2) in a time-dependent manner. Inhibition of ERK1/2 and JNK1/2 led to a significant decrease in visfatin-induced proliferation and migration of HDFs. Importantly, blocking VEGF with its neutralizing antibodies suppressed the visfatin-induced proliferation and migration of HDFs and human keratinocytes, indicating that visfatin induces the proliferation and migration of HDFs and human keratinocytes via increased VEGF expression. Moreover, visfatin effectively improved wound repair in vivo, which was comparable to the wound healing activity of epidermal growth factor (EGF). Taken together, we demonstrate that visfatin promotes the proliferation and migration of HDFs and human keratinocytes by inducing VEGF expression and can be used as a potential novel therapeutic agent for wound healing.


Author(s):  
Boris Andryukov ◽  
Natalya Besednova ◽  
Tatyana Kuznetsova ◽  
Tatyana Zaporozhets ◽  
Svetlana Ermakova ◽  
...  

Wound healing involves a complex cascade of cellular, molecular, and biochemical responses and signaling processes. It consists of successive interrelated phases, the duration of which depends on multifactorial processes. Wound treatment is a major healthcare issue that can be resolved by development of effective and affordable wound dressings based on natural materials and biologically active substances. Proper use of modern wound dressings can significantly accelerate wound healing with minimal cosmetic defects. The innovative biotechnologies for creating modern natural interactive dressings are based on sulfated polysaccharides from seaweeds with their unique structures and biological properties, the availability of their sources in the form of wild bushes, and in the form of aquaculture, as well as with a high potential for participation in process control wound healing. These natural biopolymers are a novel and promising biologically active source for designing wound dressings based on alginates, fucoidans, carrageenans, and ulvans, which serve as active and effective therapeutic tools. The aim of this review is to summarize available information about the modern wound dressing’s technologies based on seaweed-derived polysaccharides, including those successfully implemented in commercial products, with the emphasis on promising and innovative designs. The further prospect of using marine biopolymers is related to the need to analyze the results of numerous in vitro and in vivo experiments, summarize clinical trial data, develop a scientifically based approach and relevant practical recommendations for the treatment of wounds.


2018 ◽  
Vol 19 (11) ◽  
pp. 3642 ◽  
Author(s):  
Byung-Cheol Lee ◽  
Jisun Song ◽  
Arim Lee ◽  
Daeho Cho ◽  
Tae Kim

Visfatin, a member of the adipokine family, plays an important role in many metabolic and stress responses. The mechanisms underlying the direct therapeutic effects of visfatin on wound healing have not been reported yet. In this study, we examined the effects of visfatin on wound healing in vitro and in vivo. Visfatin enhanced the proliferation and migration of human dermal fibroblasts (HDFs) and keratinocytes the expression of wound healing-related vascular endothelial growth factor (VEGF) in vitro and in vivo. Treatment of HDFs with visfatin induced activation of both extracellular signal-regulated kinases 1 and 2 (ERK1/2) and c-Jun N-terminal kinases 1 and 2 (JNK1/2) in a time-dependent manner. Inhibition of ERK1/2 and JNK1/2 led to a significant decrease in visfatin-induced proliferation and migration of HDFs. Importantly, blocking VEGF with its neutralizing antibodies suppressed the visfatin-induced proliferation and migration of HDFs and human keratinocytes, indicating that visfatin induces the proliferation and migration of HDFs and human keratinocytes via increased VEGF expression. Moreover, visfatin effectively improved wound repair in vivo, which was comparable to the wound healing activity of epidermal growth factor (EGF). Taken together, we demonstrate that visfatin promotes the proliferation and migration of HDFs and human keratinocytes by inducing VEGF expression and can be used as a potential novel therapeutic agent for wound healing.


Marine Drugs ◽  
2020 ◽  
Vol 18 (10) ◽  
pp. 511
Author(s):  
Ching-Shu Lai ◽  
Chun-Wei Tu ◽  
Hsing-Chun Kuo ◽  
Pei-Pei Sun ◽  
Mei-Ling Tsai

Type II collagen is an important component of cartilage; however, little is known about its effect on skin wound healing. In this study, type II collagen was extracted from the cartilage of Acipenser baerii and its effect on in vitro and in vivo wound healing was compared to type I collagen derived from tilapia skin. Sturgeon cartilage collagen (SCC) was composed of α1 chains and with a thermal denaturation (Td) at 22.5 and melting temperature (Tm) at 72.5 °C. Coating SCC potentiated proliferation, migration, and invasion of human dermal fibroblast adult (HDFa) cells. Furthermore, SCC upregulated the gene expression of extracellular matrix (ECM) components (col Iα1, col IIIα1, elastin, and Has2) and epithelial-mesenchymal transition (EMT) molecules (N-cadherin, Snail, and MMP-1) in HDFa. Pretreatment with Akt and mitogen-activated protein kinase (MAPK) inhibitors significantly attenuated the HDFa invasion caused by SCC. In mice, the application of SCC on dorsal wounds effectively facilitated wound healing as evidenced by 40–59% wound contraction, whereas the untreated wounds were 18%. We observed that SCC reduced inflammation, promoted granulation, tissue formation, and ECM deposition, as well as re-epithelialization in skin wounds. In addition, SCC markedly upregulated the production of growth factors in the dermis, and dermal and subcutaneous white adipose tissue; in contrast, the administration of tilapia skin collagen (TSC) characterized by typical type I collagen was mainly expressed in the epidermis. Collectively, these findings indicate SCC accelerated wound healing by targeting fibroblast in vitro and in vivo.


2021 ◽  
Vol 26 (3) ◽  
pp. 2692-2699
Author(s):  
ANDREEA IOSAGEANU ◽  
◽  
ANCA OANCEA ◽  
DANIELA ILIE ◽  
ELENA DANIELA ANTON ◽  
...  

Fish bones mainly contain type I collagen and hydroxyapatite, and despite of their potential for applications in biotechnology and biomedicine, they represent one of the major source of waste generated by fish processing industry. The present study was focused on the interaction of bioactive peptides extracted from silver carp (H. molitrix) bones with human keratinocytes in culture. The potential of fish bone bioactive peptides to influence cell viability, proliferation and migration was evaluated in different experimental models in vitro. The results demonstrated a high efficiency and bioactivity of the enzymatically extracted fish bone peptides in several processes involved in cutaneous wound healing, in particular stimulation of keratinocytes metabolism and migration. In conclusion, they present a huge potential for applications in skin tissue engineering, but also in the biomedical and cosmetic fields.


2008 ◽  
Vol 105 (1) ◽  
pp. 30-36 ◽  
Author(s):  
Nasser El-Okdi ◽  
Sleiman Smaili ◽  
Vanamala Raju ◽  
Amjad Shidyak ◽  
Shalini Gupta ◽  
...  

We previously reported that cardiotonic steroids stimulate collagen synthesis by cardiac fibroblasts in a process that involves signaling through the Na-K-ATPase pathway (Elkareh et al. Hypertension 49: 215–224, 2007). In this study, we examined the effect of cardiotonic steroids on dermal fibroblasts collagen synthesis and on wound healing. Increased collagen expression by human dermal fibroblasts was noted in response to the cardiotonic steroid marinobufagenin in a dose- and time-dependent fashion. An eightfold increase in collagen synthesis was noted when cells were exposed to 10 nM marinobufagenin for 24 h ( P < 0.01). Similar increases in proline incorporation were seen following treatment with digoxin, ouabain, and marinobufagenin (10 nM × 24 h, all results P < 0.01 vs. control). The coadministration of the Src inhibitor PP2 or N-acetylcysteine completely prevented collagen stimulation by marinobufagenin. Next, we examined the effect of digoxin, ouabain, and marinobufagenin on the rate of wound closure in an in vitro model where human dermal fibroblasts cultures were wounded with a pipette tip and monitored by digital microscopy. Finally, we administered digoxin in an in vivo wound healing model. Olive oil was chosen as the digoxin carrier because of a favorable partition coefficient observed for labeled digoxin with saline. This application significantly accelerated in vivo wound healing in rats wounded with an 8-mm biopsy cut. Increased collagen accumulation was noted 9 days after wounding (both P < 0.01). The data suggest that cardiotonic steroids induce increases in collagen synthesis by dermal fibroblasts, as could potentially be exploited to accelerate wound healing.


Sign in / Sign up

Export Citation Format

Share Document