The Role of Exosomal Vimentin in Mediating Wound Healing

Despite great advances in tissue engineering and regenerative medicine,impaired wound healing is still a challenging clinical problem. Accumulating evidence demonstrates the ability of extracellular vesicles and specifically, exosomes in regenerative therapy and tissue engineering. Previous studies showed that adipose stem cell-derived exosomes have great potential in accelerating cutaneous wound healing by affecting fibroblast activities. It has been shown that vimentin serves as a coordinator of the healing process. Interestingly, vimentin has been reported to be detectable in exosomes from different cell types which we called exosomal vimentin. Therefore, we hypothesized that vimentin incorporated into the exosomes may contribute to mediating fibroblast activities in wound healing. During my Ph.D. thesis, we revealed the active and necessary role of exosomal vimentin in promoting wound healing. Our results revealed that exosomal vimentin from adipocyte progenitor cells acts as a promoter of fibroblast proliferation, migration, and ECM secretion. Our results suggested that exosomes can serve as an efficient transportation system to deliver and internalize vimentin into target cells, while vimentin could have an impact on exosome transportation, internalization, and cell communication. Furthermore, our findings revealed that during mechanical stress such as osmotic imbalance, exosomal vimentin can protect fibroblasts against stress and inhibit stress induced apoptosis. These data suggest that exosomes could be considered either as a stress modifier to restore the osmotic balance or as a conveyer of stress to induce osmotic stress-driven conditions. In conclusion, our in vitro and in vivo experiments provide evidence that exosomal vimentin shortens the healing time and reduces scar formation.Trots stora framsteg inom vävnadsteknik och regenerativ medicin, så är försämrad sårläkning fortfarande ett stort problem inom klinisk medicin. Det finns allt starkare belägg för att extracellulära vesikler, särskilt exosomer, har sårläkande förmåga i samband med regenerativ terapi och vävnadsteknik. Tidigare studier har visat att exosomer som härrör sig från adipocyta stamceller har stort potential i påskyndandet av hudens sårläkning genom deras förmåga att påverka aktiviteten hos fibroblaster. Man har visat att vimentin fungerar som en koordinator för läkningsprocessen. Vi har kunnat påvisa närvaro av vimentin i exosomer från olika celltyper, som vi kallar exosomalt vimentin. Därmed antog vi att vimentin inkorporerat i exosomer kunde bidra till förmedlingen av fibroblastaktiviteten vid sårläkning. Under mitt doktorsarbete har vi påvisat exosomalt vimentin är nödvändigt för att främja sårläkning. Våra resultat visade att exosomalt vimentin från adipocyt-progenitorceller stimulerar fibroblastproliferation, migration och ECM-sekretion. Våra resultat antydde att exosomer kan fungera som ett effektivt system för att transportera och internalisera vimentin i målceller, medan vimentin i sin tur kan ha en inverkan på exosomtransport, internalisering och cellulär kommunikation. Dessutom visade våra resultat att exosomalt vimentin under mekanisk stress, såsom osmotisk obalans, kan skydda fibroblaster mot stress och hämma stressinducerad apoptos. Dessa data indikerar att exosomer kan betraktas antingen som stressmodifierare för att återställa osmotisk balans eller som en stressbärare för att inducera osmotiska stressdrivna tillstånd. Sammanfattningsvis visar våra experiment, både in vitro och in vivo, att exosomalt vimentin försnabbar sårläkning på ett signifikant vis och att det även minskar ärrbildning

The molecular biophysics of extracellular vimentin and its role in pathogen–host interactions

Vimentin, an intermediate filament protein typically located in the cytoplasm of mesenchymal cells, can also be secreted as an extracellular protein. The organization of extracellular vimentin strongly determines its functions in physiological and pathological conditions, making it a promising target for future therapeutic interventions. The extracellular form of vimentin has been found to play a role in the interaction between host cells and pathogens. In this review, we first discuss the molecular biophysics of extracellular vimentin, including its structure, secretion, and adhesion properties. We then provide a general overview of the role of extracellular vimentin in mediating pathogen-host interactions, with a focus on its interactions with viruses and bacteria. We also discuss the implications of these findings for the development of new therapeutic strategies for combating infectious diseases

Vimentin takes a hike – Emerging roles of extracellular vimentin in cancer and wound healing

Vimentin is a cytoskeletal protein important for many cellular processes, including proliferation, migration, invasion, stress resistance, signaling, and many more. The vimentin-deficient mouse has revealed many of these functions as it has numerous severe phenotypes, many of which are found only following a suitable challenge or stress. While these functions are usually related to vimentin as a major intracellular protein, vimentin is also emerging as an extracellular protein, exposed at the cell surface in an oligomeric form or secreted to the extracellular environment in soluble and vesicle-bound forms. Thus, this review explores the roles of the extracellular pool of vimentin (eVIM), identified in both normal and pathological states. It focuses specifically on the recent advances regarding the role of eVIM in wound healing and cancer. Finally, it discusses new technologies and future perspectives for the clinical application of eVIM

Exosomal Vimentin from Adipocyte Progenitors Protects Fibroblasts against Osmotic Stress and Inhibits Apoptosis to Enhance Wound Healing

Mechanical stress following injury regulates the quality and speed of wound healing. Improper mechanotransduction can lead to impaired wound healing and scar formation. Vimentin intermediate filaments control fibroblasts' response to mechanical stress and lack of vimentin makes cells significantly vulnerable to environmental stress. We previously reported the involvement of exosomal vimentin in mediating wound healing. Here we performed in vitro and in vivo experiments to explore the effect of wide-type and vimentin knockout exosomes in accelerating wound healing under osmotic stress condition. Our results showed that osmotic stress increases the size and enhances the release of exosomes. Furthermore, our findings revealed that exosomal vimentin enhances wound healing by protecting fibroblasts against osmotic stress and inhibiting stress-induced apoptosis. These data suggest that exosomes could be considered either as a stress modifier to restore the osmotic balance or as a conveyer of stress to induce osmotic stress-driven conditions

Exosomal Vimentin from Adipocyte Progenitors Protects Fibroblasts against Osmotic Stress and Inhibits Apoptosis to Enhance Wound Healing

Mechanical stress following injury regulates the quality and speed of wound healing. Improper mechanotransduction can lead to impaired wound healing and scar formation. Vimentin intermediate filaments control fibroblasts’ response to mechanical stress and lack of vimentin makes cells significantly vulnerable to environmental stress. We previously reported the involvement of exosomal vimentin in mediating wound healing. Here we performed in vitro and in vivo experiments to explore the effect of wide-type and vimentin knockout exosomes in accelerating wound healing under osmotic stress condition. Our results showed that osmotic stress increases the size and enhances the release of exosomes. Furthermore, our findings revealed that exosomal vimentin enhances wound healing by protecting fibroblasts against osmotic stress and inhibiting stress-induced apoptosis. These data suggest that exosomes could be considered either as a stress modifier to restore the osmotic balance or as a conveyer of stress to induce osmotic stress-driven conditions

Multifunctional nanoparticle developments in cancer diagnosis and treatment

Nanotechnology, although still in the early stages, has the potential to revolutionize the early diagnosis, treatment, and monitoring of disease progression. Technological application of nanometer molecules in medicine with the aim of fighting and curing ailments is the globally definition of nanomedicine. The success of nanotechnology in the healthcare part is driven by the possibility to work at the same scale of several biological processes, cellular mechanisms, and organic molecules. With the growing understanding of methods to functionalize nanoparticles and the continued efforts of creative scientists to advance this technology, it is likely that functionalized nanoparticles will become an important tool in the above mentioned areas. This paper describes the role of multifunctional nanoparticle in diagnosis and treatment of cancer. Therefore, the aim of this review is to provide basic information on nanoparticles, describe previously developed methods to functionalize nanoparticles and discuss their potential applications in biomedical sciences and finally mention the therapeutic nanoparticle commercialization challenges. Keywords: Multifunctional nanoparticle, Cancer, Diagnosis, Treatment, Therap

Simultaneous expression of 5-enol pyruvyl shikimate 3-phosphate synthase (epsps) and glyphosate oxidoreductase (gox) in transgenic canola plants towards enhancing resistance to glyphosate herbicide

Canola (Brassica napus L.) is known as one of the most important oil-producing plants worldwide that has a high food value. Today, expansion of planting area of this plant has been highly considered. The presence of weeds in canola fields causes a significant loss in crop yield and quality. So far, the most widely herbicide used to manage weeds is the broad spectrum glyphosate that targets 5 enolpyruvylshikimate-3-phosphate synthase (EPSPS) enzyme.  In this study, with the aim of identification of new strategies to develop herbicides-resistant plants, Glyphosate Oxidoreductase (gox) and epsps genes under the control of CaMV 35S promoter were transferred to canola seedlings with pBI121 expression vector, to develop new plants with higher herbicide resistance level. Acquired seedlings were screened and then subjected to herbicide resistance bioassay. Molecular analysis of transgenic lines through PCR and RT-PCR showed successful integration and expression of the transgene, respectively. Result showed the higher relative resistance of the transgenic lines expressing two gene cassettes compared to single gene cassette lines. This study suggests that simultaneous application of two different strategies can lead to more glyphosate-resistance to develop new genetically modified crops specifically in oilseed plants such as canola