purification-characterization-extracellular-vesicles-from-human

Purification and Characterization of Extracellular Vesicles from Human Adipose-Derived Mesenchymal Stem Cells

Human adipose-derived mesenchymal stem cells (ADSCs) can promote the regeneration and reconstruction of various tissues and organs. Recent research ...

Chinese PLA general hospital

Chinese PLA General Hospital

We previously reported that co-transplantation of exosomes from hypoxia-preconditioned adipose mesenchymal stem cells (ADSCs) improves the neoangiogenesis and survival of the grafted tissue. This study aimed to investigate the molecular mechanism of this protective effect.

Exosomes from hypoxia-treated human adipose-derived mesenchymal stem cells enhance angiogenesis through VEGF/VEGF-R.

The targeted delivery of therapeutic agents to secondary lymphoid organs (SLOs), which are the niches for immune initiation, provides an unprecedented opportunity for immune intolerance induction. The alloimmune rejection postvascularized composite allotransplantation (VCA) is mediated by T lymphocytes. Human adipose-derived stem cells (hASCs) possess the superiority of convenient availability and potent immunoregulatory property, but their therapeutic results in the VCA are unambiguous thus far. Chemokine receptor 7 (CCR7) can specifically guide immune cells migrating into SLOs. There, the genes of CCR7-GFP or GFP alone were introduced into hASCs by lentivirus. hASCs/CCR7 maintained the multidifferentiation and immunoregulatory abilities, but it gained the migration capacity elicited by secondary lymphoid organ chemokine (SCL) (CCR7 ligand) in vitro. Noteworthily, intravenously infused hASCs/CCR7 targetedly relocated in the T-cell aggression area in SLOs. In a rat VCA model, hASCs/GFP transfusion had a rare effect on the allografted vascularized composite. However, hASCs/CCR7 infusion potently prolonged the grafts' survival time. The ameliorated pathologic exhibition and the regulated inflammatory cytokines in the peripheral blood were also observed. The altered axis of Th1/Th2 and Tregs/Th17 in SLOs may underlie the downregulated rejection response. Moreover, the proteomic examination of splenic T lymphocytes also confirmed that hASCs/CCR7 decreased the proteins related to cytokinesis, lymphocyte proliferation, differentiation, and apoptotic process. In conclusion, our present study demonstrated that targeted migration of hASCs/CCR7 to SLOs highly intensifies their in vivo immunomodulatory effect in the VCA model for the first time. We believe this SLO-targeting strategy may improve the clinical therapeutic efficacy of hASC for allogeneic and autogenic immune disease. Stem Cells 2019;37:1581-1594.

Targeted Migration of Human Adipose-Derived Stem Cells to Secondary Lymphoid Organs Enhances Their Immunomodulatory Effect and Prolongs the Survival of Allografted Vascularized Composites.

Biological scaffolds based stem cell delivery methods have emerged as a promising approach for tissue repair and regeneration. Here we developed a hydrogel biological scaffold from human decellularized adipose matrix (hDAM) for human adipose-derived stem cells (hASCs) delivery to accelerate chronic wound healing. The hDAM hydrogel was prepared by pepsin mediated digestion and pH controlled neutralization. The morphology, survival, proliferation, and angiogenic paracrine activity of hASCs cultured in the hydrogel were assessed. Moreover, the therapeutic efficacy of the hASCs-hydrogel composite for impaired wound healing was evaluated by using a full-thickness wound model on diabetic mouse. The developed hDAM hydrogel was a thermosensitive hydrogel, presented the biochemical complexity of native extracellular matrix and formed a porous nanofiber structure after gelation. The hydrogel can support hASCs adhesion, survival, and proliferation. Compared to standard culture condition, hASCs cultured in the hydrogel exhibited enhanced paracrine activity with increased secretion of hepatocyte growth factor. In the diabetic mice model with excisional full-thickness skin wounds, mice treated with the hASCs-hydrogel composite displayed accelerated wound closure and increased neovascularization. Our results suggested that the developed hDAM hydrogel can provide a favorable microenvironment for hASCs with augmented regeneration potential to accelerate chronic wound healing.

Human decellularized adipose matrix derived hydrogel assists mesenchymal stem cells delivery and accelerates chronic wound healing.

Although osteoporosis is associated with increased risks of complications of fracture fixation in the orthopedic literature, the association between local bone quality (LBQ) and complications of facial fracture fixation is unknown. The authors aim to identify that if decreased LBQ is an independent risk factor for complications following facial fracture fixation?

Is Decreased Local Bone Quality an Independent Risk Factor for Complications Following Fracture Fixation of Facial Bones.

Invited Commentary from the authors of: Han Y, et al. Free Medial Plantar Flap Versus Free Dorsal Myocutaneous Flap for the Reconstruction of Traumatic Foot Sole Defects.

Although external circular frame (ECF) has been widely used for the correction of knee and ankle deformities, few studies reported the use of ECF for the treatment of severe postburn elbow contracture and stiffness (SPECS). The purpose of this retrospective study was to investigate the effectiveness and safety of the distraction using ECF in treating SPECS.

Treatment of Severe Postburn Contracture of the Elbow via Distraction With External Circular Frame in Pediatric Patient.

Recent studies showed that exosomes obtained from adipose-derived stem cells (ADSCs) could improve the angiogenesis of fat grafts via overexpression of vascular endothelial growth factor (VEGF). Human antigen R (HuR) promotes the expression of VEGF in many cancers, but the effect of HuR in normal endothelial cells in the presence of ADSC-derived exosomes remains unclear. We aimed to investigate the effect of HuR on the expression of VEGF and angiogenesis of human umbilical vein endothelial cells (HUVECs) cultured with ADSCs-derived exosomes. The HuR-overexpressed HUVECs (HuR-HUVECs) were cocultured with ADSCs-derived exosomes. qRT-PCR and Western blotting were performed to examine the stability and expression of VEGF-A mRNA and protein. The proliferation, migration, and proangiogenic capacity of HuR-HUVECs were evaluated using cell counting kit-8 (CCK-8), scratch wound healing, and Matrigel tube formation assay. qRT-PCR showed that HuR-HUVECs had higher expression and slower attenuation of VEGF-A mRNA. Western blotting confirmed higher expression of VEGF-A in HuR-HUVECs. CCK-8, scratch wound healing, and Matrigel tube formation assay demonstrated an increased proangiogenic effect in HuR-HUVECs. HuR promotes angiogenesis of HUVECs cocultured with ADSCs-derived exosomes via stabilization and overexpression of VEGF in vitro. The HuR/VEGF pathway is an important regulatory mechanism of angiogenesis in endothelial cells.

Human antigen R promotes angiogenesis of endothelial cells cultured with adipose stem cells derived exosomes via overexpression of vascular endothelial growth factor in vitro.

An active role of reconstructive surgeon in otologic tumor surgery.

To explore the effectiveness of two-stage operation on free latissimus dorsi myocutaneous flap transplantation and skull contour reconstruction in the treatment of head titanium mesh exposure complicated with soft tissue infection.

[Application of two-stage operation on free latissimus dorsi myocutaneous flap transplantation and skull contour reconstruction in treatment of head titanium mesh exposure with soft tissue infection].

Cartilage is an important tissue that is widely found in joints, ears, nose and other organs. The limited capacity to regenerate makes cartilage reconstruction an urgent clinical demand. Due to the avascular nature of cartilage, we hypothesized that inhibition of vascularization contributes to cartilage formation. Here, we used VEGFa siRNA to inhibit the infiltration of the local vascular system. Optimized lipid nanoparticles were prepared by microfluidics for the delivery of siRNA. Then, we constructed a tissue engineering scaffold. Both seed cells and VEGFa siRNA-LNPs were loaded in a GELMA hydrogel. Subcutaneous implantation experiments in nude mice indicate that this is a promising strategy for cartilage reconstruction. The regenerated cartilage was superior, with significant upregulation of SOX9, COL-II and ACAN. This is attributed to an environment deficient in oxygen and nutrients, which facilitates cartilage formation by upregulating HIF-1α and FOXO transcription factors. In conclusion, a GelMA/Cells+VEGFa siRNA-LNPs scaffold was constructed to achieve superior cartilage regeneration.

Lipid nanoparticle-encapsulated VEGFa siRNA facilitates cartilage formation by suppressing angiogenesis.

The reconstruction of large fistulous defects following the radical ablation of maxillary sinus carcinoma remains challenging. The procedure requires not only the coverage of both intra-nasal lining and cheek skin but also sufficient obliteration of dead space between the two surfaces. In this report, we present our experience on the reconstruction of through-and-through defects in the mid-face with poly-foliated chimeric perforator flaps.

One stage reconstruction of mid-face fistulous defects after maxillary sinus carcinoma resection with chimeric perforator free flaps.

To review the research progress of new antibacterial hydrogels in the treatment of infected wounds in the field of biomedicine, in order to provide new methods and ideas for clinical treatment of infected wounds.

Article	Year
Exosomes from hypoxia-treated human adipose-derived mesenchymal stem cells enhance angiogenesis through VEGF/VEGF-R. The international journal of biochemistry & cell biology\| PubMed ID: 30710751	2019
Targeted Migration of Human Adipose-Derived Stem Cells to Secondary Lymphoid Organs Enhances Their Immunomodulatory Effect and Prolongs the Survival of Allografted Vascularized Composites. Stem cells (Dayton, Ohio)\| PubMed ID: 31414513	2019
Human decellularized adipose matrix derived hydrogel assists mesenchymal stem cells delivery and accelerates chronic wound healing. Journal of biomedical materials research. Part A\| PubMed ID: 33253453	2021
Is Decreased Local Bone Quality an Independent Risk Factor for Complications Following Fracture Fixation of Facial Bones. The Journal of craniofacial surgery\| PubMed ID: 33427779	2021
Invited Commentary from the authors of: Han Y, et al. Free Medial Plantar Flap Versus Free Dorsal Myocutaneous Flap for the Reconstruction of Traumatic Foot Sole Defects. Annals of plastic surgery\| PubMed ID: 33661228	2022
Treatment of Severe Postburn Contracture of the Elbow via Distraction With External Circular Frame in Pediatric Patient. Annals of plastic surgery\| PubMed ID: 34397514	2021
Human antigen R promotes angiogenesis of endothelial cells cultured with adipose stem cells derived exosomes via overexpression of vascular endothelial growth factor in vitro. Adipocyte\| PubMed ID: 34635021	2021
An active role of reconstructive surgeon in otologic tumor surgery. Ear, nose, & throat journal\| PubMed ID: 34818935	2021
[Application of two-stage operation on free latissimus dorsi myocutaneous flap transplantation and skull contour reconstruction in treatment of head titanium mesh exposure with soft tissue i... Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery\| PubMed ID: 35848178	2022
Lipid nanoparticle-encapsulated VEGFa siRNA facilitates cartilage formation by suppressing angiogenesis. International journal of biological macromolecules\| PubMed ID: 36108749	2022
One stage reconstruction of mid-face fistulous defects after maxillary sinus carcinoma resection with chimeric perforator free flaps. Microsurgery\| PubMed ID: 36530044	2023
[Research progress of antibacterial hydrogel in treatment of infected wounds]. Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery\| PubMed ID: 38385240	2024

Yudi Han

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