Exosomal DMBT1 from human urine-derived stem cells facilitates diabetic wound repair by promoting angiogenesis

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Chronic non-healing wounds represent one of the most common complications of diabetes and need advanced treatment strategies. Exosomes are key mediators of cell paracrine action and can be directly utilized as therapeutic agents for tissue repair and regeneration. Here, we explored the effects of exosomes from human urine-derived stem cells (USC-Exos) on diabetic wound healing and the underlying mechanism.

Methods: USCs were characterized by flow cytometry and multipotent differentiation potential analyses. USC-Exos were isolated from the conditioned media of USCs and identified by transmission electron microscopy and flow cytometry. A series of functional assays in vitro were performed to assess the effects of USC-Exos on the activities of wound healing-related cells. Protein profiles in USC-Exos and USCs were examined to screen the candidate molecules that mediate USC-Exos function. The effects of USC-Exos on wound healing in streptozotocin-induced diabetic mice were tested by measuring wound closure rates, histological and immunofluorescence analyses. Meanwhile, the role of the candidate protein in USC-Exos-induced regulation of angiogenic activities of endothelial cells and diabetic wound healing was assessed.

Results: USCs were positive for CD29, CD44, CD73 and CD90, but negative for CD34 and CD45. USCs were able to differentiate into osteoblasts, adipocytes and chondrocytes. USC-Exos exhibited a cup- or sphere-shaped morphology with a mean diameter of 51.57 ± 2.93 nm and positive for CD63 and TSG101. USC-Exos could augment the functional properties of wound healing-related cells including the angiogenic activities of endothelial cells. USC-Exos were enriched in the proteins that are involved in regulation of wound healing-related biological processes. Particularly, a pro-angiogenic protein called deleted in malignant brain tumors 1 (DMBT1) was highly expressed in USC-Exos. Further functional assays showed that DMBT1 protein was required for USC-Exos-induced promotion of angiogenic responses of cultured endothelial cells, as well as angiogenesis and wound healing in diabetic mice.

Conclusion: Our findings suggest that USC-Exos may represent a promising strategy for diabetic soft tissue wound healing by promoting angiogenesis via transferring DMBT1 protein.

Related collections

Most cited references 36

Record: found
Abstract: found
Article: not found

Coupling of angiogenesis and osteogenesis by a specific vessel subtype in bone.

Anjali P. Kusumbe, Saravana K. Ramasamy, Ralf H. Adams (2014)

The mammalian skeletal system harbours a hierarchical system of mesenchymal stem cells, osteoprogenitors and osteoblasts sustaining lifelong bone formation. Osteogenesis is indispensable for the homeostatic renewal of bone as well as regenerative fracture healing, but these processes frequently decline in ageing organisms, leading to loss of bone mass and increased fracture incidence. Evidence indicates that the growth of blood vessels in bone and osteogenesis are coupled, but relatively little is known about the underlying cellular and molecular mechanisms. Here we identify a new capillary subtype in the murine skeletal system with distinct morphological, molecular and functional properties. These vessels are found in specific locations, mediate growth of the bone vasculature, generate distinct metabolic and molecular microenvironments, maintain perivascular osteoprogenitors and couple angiogenesis to osteogenesis. The abundance of these vessels and associated osteoprogenitors was strongly reduced in bone from aged animals, and pharmacological reversal of this decline allowed the restoration of bone mass.

0 comments Cited 718 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Distinct fibroblast lineages determine dermal architecture in skin development and repair

Ryan R. Driskell, Beate M Lichtenberger, Esther Hoste … (2013)

Fibroblasts are the major mesenchymal cell type in connective tissue and deposit the collagen and elastic fibers of the extracellular matrix (ECM) 1 . Even within a single tissue fibroblasts exhibit remarkable functional diversity, but it is not known whether this reflects the existence of a differentiation hierarchy or is a response to different environmental factors. Here we show, using transplantation assays and lineage tracing, that the fibroblasts of skin connective tissue arise from two distinct lineages. One forms the upper dermis, including the dermal papilla that regulates hair growth and the arrector pili muscle (APM), which controls piloerection. The other forms the lower dermis, including the reticular fibroblasts that synthesise the bulk of the fibrillar ECM, and the pre-adipocytes and adipocytes of the hypodermis. The upper lineage is required for hair follicle formation. In wounded adult skin, the initial wave of dermal repair is mediated by the lower lineage and upper dermal fibroblasts are recruited only during re-epithelialisation. Epidermal beta-catenin activation stimulates expansion of the upper dermal lineage, rendering wounds permissive for hair follicle formation. Our findings explain why wounding is linked to formation of ECM-rich scar tissue that lacks hair follicles 2-4 . They also form a platform for discovering fibroblast lineages in other tissues and for examining fibroblast changes in ageing and disease.

0 comments Cited 438 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Exosomes derived from miR-140-5p-overexpressing human synovial mesenchymal stem cells enhance cartilage tissue regeneration and prevent osteoarthritis of the knee in a rat model

Shi-Cong Tao, TING YUAN, Yue-Lei Zhang … (2017)

OBJECTIVES: Osteoarthritis (OA) is the most common joint disease throughout the world. Exosomes derived from miR-140-5p-overexpressing synovial mesenchymal stem cells (SMSC-140s) may be effective in treating OA. We hypothesized that exosomes derived from SMSC-140 (SMSC-140-Exos) would enhance the proliferation and migration abilities of articular chondrocytes (ACs) without harming extracellular matrix (ECM) secretion. METHODS: SMSCs were transfected with or without miR-140-5p. Exosomes derived from SMSCs or SMSC-140s (SMSC-Exos or SMSC-140-Exos) were isolated and identified. Proliferation, migration and ECM secretion were measured in vitro and compared between groups. The mechanism involving alternative Wnt signalling and activation of Yes-associated protein (YAP) was investigated using lentivirus, oligonucleotides or chemical drugs. The preventative effect of exosomes in vivo was measured using Safranin-O and Fast green staining and immunohistochemical staining. RESULTS: Wnt5a and Wnt5b carried by exosomes activated YAP via the alternative Wnt signalling pathway and enhanced proliferation and migration of chondrocytes with the side-effect of significantly decreasing ECM secretion. Highly-expressed miR-140-5p blocked this side-effect via RalA. SMSC-140-Exos enhanced the proliferation and migration of ACs without damaging ECM secretion in vitro, while in vivo, SMSC-140-Exos successfully prevented OA in a rat model. CONCLUSIONS: These findings highlight the promising potential of SMSC-140-Exos in preventing OA. We first found a potential source of exosomes and studied their merits and shortcomings. Based on our understanding of the molecular mechanism, we overcame the shortcomings by modifying the exosomes. Such exosomes derived from modified cells hold potential as future therapeutic strategies.

0 comments Cited 291 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Journal

Journal ID (nlm-ta): Theranostics

Journal ID (iso-abbrev): Theranostics

Journal ID (publisher-id): thno

Title: Theranostics

Publisher: Ivyspring International Publisher (Sydney )

ISSN (Electronic): 1838-7640

Publication date Collection: 2018

Publication date (Electronic): 7 February 2018

Volume: 8

Issue: 6

Pages: 1607-1623

Affiliations

[1 ]Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.

[2 ]Hunan Key Laboratory of Organ Injury, Aging and Regenerative Medicine, Changsha, Hunan, China.

[3 ]Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.

[4 ]Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.

[5 ]Department of Spine Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.

[6 ]Xiangya Nursing School, Central South University, Changsha, Hunan 410013, China

[7 ]Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China

[8 ]China Orthopedic Regenerative Medicine Group (CORMed), Changsha, Hunan, China.

Author notes

✉ Corresponding author: Hui Xie: huixie@ 123456csu.edu.cn ; #88 Xiangya Road, Changsha, 410008, PR China; Tel: 86-0731-84327068

* Chun-Yuan Chen and Shan-Shan Rao contributed equally to this work.

Competing Interests: The authors have declared that no competing interest exists.

Article

Publisher ID: thnov08p1607

DOI: 10.7150/thno.22958

PMC ID: 5858170

PubMed ID: 29556344

SO-VID: 5c3b12d7-1cc1-4dfc-a0e9-08555991eadc

License:

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license ( https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.

Exosomal DMBT1 from human urine-derived stem cells facilitates diabetic wound repair by promoting angiogenesis

Read this article at

Abstract

Related collections

Bacterial extracellular vesicles

Most cited references 36

Coupling of angiogenesis and osteogenesis by a specific vessel subtype in bone.

Distinct fibroblast lineages determine dermal architecture in skin development and repair

Exosomes derived from miR-140-5p-overexpressing human synovial mesenchymal stem cells enhance cartilage tissue regeneration and prevent osteoarthritis of the knee in a rat model

Author and article information

Journal

Affiliations

Author notes

Article

History

Categories

Comments

Comment on this article

Similar content 268

Cited by 171

Most referenced authors 777