Stem cell‐derived exosomes: A promising strategy for fracture healing

Hao, Zichen; Lü, Jun; Wang, Shan-Zheng; Wu, Hao; Zhang, Yuntong; Xu, Shuogui

doi:10.1111/cpr.12359

Cited by 86 publications

(65 citation statements)

References 110 publications

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“…During the past few years, mounting evidence has demonstrated that exosomes derived from different stem cells could promote bone regeneration ; thus, exosome therapies exhibit great potential for clinical translation . It is believed that the surface proteins and the cargo of exosomes are crucial to their function .…”

Section: Discussionmentioning

confidence: 99%

“…Consistent with the findings in BMSCs , in the present study, we demonstrate that the pro‐osteogenic and proangiogenic effects of BMSC‐exos are also impaired by T1DM. As mentioned above, it is widely acknowledged that exosomes promote tissue regeneration by transferring functional cargo consisting of genetic information (RNA and DNA), proteins and other molecules to target cells, thereby regulating the bioactivity of the recipient cells . Thus, the components present in BMSC‐exos may have changed in T1DM condition.…”

Section: Discussionmentioning

confidence: 99%

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Impaired Bone Regenerative Effect of Exosomes Derived from Bone Marrow Mesenchymal Stem Cells in Type 1 Diabetes

Zhu

Jia

Wang

et al. 2019

Stem Cells Translational Medicine

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Stem cell‐derived exosomes have exhibited promise for applications in tissue regeneration. However, one major problem for stem cell‐derived exosome therapies is identifying appropriate source cells. In the present study, we aimed to compare the bone regenerative effect of exosomes secreted by bone marrow mesenchymal stem cells (BMSCs) derived from type 1 diabetes rats (dBMSC‐exos) and exosomes secreted by BMSCs derived from normal rats (nBMSC‐exos). BMSCs were isolated from rats with streptozotocin‐induced diabetes and normal rats. dBMSC‐exos and nBMSC‐exos were isolated by an ultracentrifugation method and identified. The effects of dBMSC‐exos and nBMSC‐exos on the proliferation and migration of BMSCs and human umbilical vein endothelial cells (HUVECs) were investigated. The effects of exosomes on the osteogenic differentiation of BMSCs and the angiogenic activity of HUVECs were compared. Finally, a rat calvarial defect model was used to compare the effects of exosomes on bone regeneration and neovascularization in vivo. In vitro, dBMSC‐exos and nBMSC‐exos both enhanced the osteogenic differentiation of BMSCs and promoted the angiogenic activity of HUVECs, but nBMSC‐exos had a greater effect than dBMSC‐exos. Similarly, in vivo, both dBMSC‐exos and nBMSC‐exos promoted bone regeneration and neovascularization in rat calvarial defects, but the therapeutic effect of nBMSC‐exos was superior to that of dBMSC‐exos. The present study demonstrates for the first time that the bone regenerative effect of exosomes derived from BMSCs is impaired in type 1 diabetes, indicating that for patients with type 1 diabetes, the autologous transplantation of BMSC‐exos to promote bone regeneration may be inappropriate. stem cells translational medicine 2019;8:593–605

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Impaired Bone Regenerative Effect of Exosomes Derived from Bone Marrow Mesenchymal Stem Cells in Type 1 Diabetes

Zhu

Jia

Wang

et al. 2019

Stem Cells Translational Medicine

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“…Exosomes derived from MSCs show great potential in different fields of regenerative medicine, ranging from neural to skeletal regeneration. 14,15 A study in vitro demonstrated that EVs derived from bone-marrow MSCs (BMSCs) were able to enter the osteoblast and positively regulate osteoblastic differentiation. 16 In line with this result and also in vivo studies, EVs derived from different types of MSCs, including BMSCs and embryonic MSCs, have been reported to facilitate the processes of fracture healing, osteochondral regeneration, and calvarial bone-defect repair.…”

Section: Introductionmentioning

confidence: 99%

A novel role in skeletal segment regeneration of extracellular vesicles released from periodontal-ligament stem cells

Diomede

D’Aurora

Gugliandolo

et al. 2018

IJN

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PurposeThe combination of oral derived stem cells and 3-D scaffolds is considered advantageous in bone repair. In particular, collagen membranes possess ideal biological properties and can support infiltration and proliferation of osteoblasts, promoting bone regeneration. Our study aimed to develop a new biocompatible osteogenic construct composed of a commercially available collagen membrane (Evolution [Evo]), human periodontal-ligament stem cells (hPDLSCs) enriched with extracellular vesicles (EVs), or polyethylenimine (PEI)-engineered EVs (PEI-EVs).MethodsOsteogenic ability and expression of osteogenic genes were evaluated in vitro in hPDLSCs cultured with or without Evo, with Evo and EVs, or PEI-EVs. In addition, the bone-regeneration capacity of Evo, Evo enriched with hPDLSCs, Evo enriched with hPDLSCs and EVs/PEI-EVs was investigated in rats subjected to calvarial defects.ResultsOur results showed that Evo enriched with EVs and PEI-EVs showed high biocompatibility and osteogenic properties in vitro and in vivo. In addition, quantitative reverse-transcription polymerase chain reaction demonstrated the upregulation of osteogenic genes, such as TGFB1, MMP8, TUFT1, TFIP11, BMP2, and BMP4, in the presence of PEI-EVs. Upregulation of BMP2/4 was confirmed for Evo enriched with PEI-EVs and hPDLSCs both in vitro by Western blot and in vivo by immunofluorescence.ConclusionOur results indicated that Evo enriched with hPDLSCs and PEI-EVs is able to promote a bone-regeneration process for the treatment of calvarium and ossification defects caused by accidental or surgery trauma. In particular, PEI-EVs had a significant role in activation of the osteogenic process.

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“…In addition, exosome treatment can improve renal function in a mouse model of acute kidney injury [57]. These studies indicate that exosomes have the capacity to promote tissue regeneration, which provides a basis for their potential application in bone regeneration [58].…”

Section: A Brief Overview Of Exosomementioning

confidence: 90%

Potential Therapeutic Applications of Exosomes in Bone Regenerative Medicine

Yang¹,

Zhu²,

Lu³

et al. 2019

Osteogenesis and Bone Regeneration

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The ability of bone regeneration is relatively robust, which is crucial for fracture healing, but delayed healing and nonunion are still common problems in clinical practice. Fortunately, exciting results have been achieved for regenerative medicine in recent years, especially in the area of stem cell-based treatment, but all these cell-based approaches face challenging problems, including immune rejection. For this reason, exosomes, stem cell-derived small vesicles of endocytic origin, have attracted the attention of many investigators in the field of bone regeneration. One of the attractive features of exosomes is that they are small and can travel between cells and deliver bioactive products, including miRNA, mRNA, proteins, and various other factors, to promote bone regeneration, with undetectable immune rejection. In this chapter, we intend to briefly update the recent progressions, and discuss the potential challenges in the target areas. Hopefully, our discussion would be helpful not only for the clinicians and the researchers in the specific disciplines but also for the general audiences as well.

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Stem cell‐derived exosomes: A promising strategy for fracture healing

Cited by 86 publications

References 110 publications

Impaired Bone Regenerative Effect of Exosomes Derived from Bone Marrow Mesenchymal Stem Cells in Type 1 Diabetes

Impaired Bone Regenerative Effect of Exosomes Derived from Bone Marrow Mesenchymal Stem Cells in Type 1 Diabetes

A novel role in skeletal segment regeneration of extracellular vesicles released from periodontal-ligament stem cells

Potential Therapeutic Applications of Exosomes in Bone Regenerative Medicine

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