Evidence map›Paper›PMID 40484285›Full record

ArticleJournal of controlled release : official journal of the Controlled Release Society2025

Targeted delivery of engineered extracellular vesicles to simultaneously promote vascularization and muscle regeneration in ischemic limbs.

Ting Zhong, Ning Gao, Hong Niu, Ya Guan, Jiaxing Wen, Zhongting Liu, Jianjun Guan

Abstract read
In one paragraph

Article in Journal of controlled release : official journal of the Controlled Release Society, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Review
  3. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Ting ZhongDepartment of Mechanical Engineering & Materials Science, McKelvey School of Engineering, Washington University in St. Louis, St. Louis, MO, USA.
Ning GaoInstitute of Materials Science and Engineering, McKelvey School of Engineering, Washington University in St. Louis, St. Louis, MO, USA.
Hong NiuDepartment of Mechanical Engineering & Materials Science, McKelvey School of Engineering, Washington University in St. Louis, St. Louis, MO, USA.
Ya GuanInstitute of Materials Science and Engineering, McKelvey School of Engineering, Washington University in St. Louis, St. Louis, MO, USA.
Jiaxing WenInstitute of Materials Science and Engineering, McKelvey School of Engineering, Washington University in St. Louis, St. Louis, MO, USA.
Zhongting LiuInstitute of Materials Science and Engineering, McKelvey School of Engineering, Washington University in St. Louis, St. Louis, MO, USA.
Jianjun GuanDepartment of Mechanical Engineering & Materials Science, McKelvey School of Engineering, Washington University in St. Louis, St. Louis, MO, USA; Institute of Materials Science and Engineering, McKelvey School of Engineering, Washington University in St. Louis, St. Louis, MO, USA; Department of Biomedical Engineering, McKelvey School of Engineering, Washington University in St. Louis, St. Louis, MO, USA. Electronic address: jguan22@wustl.edu.

Funding

Targeting angiogenesis for fracture nonunion treatment under inflammatory diseasesR01AR077616 · NIAMS · WASHINGTON UNIVERSITY · PI GUAN, JIANJUN, SHEN, JIE · 2020 to 2025
$2.7M
Hydrogel encapsulation of a tissue repair protein to treat chronic woundsR01AG056919 · NIA · OHIO STATE UNIVERSITY · PI GUAN, JIANJUN, LI, HAICHANG · 2017 to 2021
$2.4M
Targeted delivery of a proangiogenic and promyogenic protein for regeneration of diabetic ischemic limbsR01HL164062 · NHLBI · WASHINGTON UNIVERSITY · PI GUAN, JIANJUN, ZHANG, FUZHONG · 2022 to 2025
$2.3M
Preservation and Vascularization of Cardiac Extracellular Matrix after Myocardial InfarctionR01HL138175 · NHLBI · WASHINGTON UNIVERSITY · PI GUAN, JIANJUN · 2019 to 2022
$1.8M
Regenerative wound dressings for accelerating diabetic wound healingR01DK133949 · NIDDK · WASHINGTON UNIVERSITY · PI GUAN, JIANJUN · 2022 to 2025
$1.8M
Engineered nanoparticles to control inflammation and fibrosis after acute myocardial infarctionR01HL174055 · NHLBI · WASHINGTON UNIVERSITY · PI Jianjun Guan · 2024 to 2026
$1.6M
Stem Cell Oxygenation and Ischemic Tissue RegenerationR01HL138353 · NHLBI · WASHINGTON UNIVERSITY · PI GUAN, JIANJUN · 2017 to 2020
$1.5M
CONTROL OF CARDIAC FIBROSIS TO PREVENT CARDIAC FUNCTION DETERIORATIONR01EB022018 · NIBIB · WASHINGTON UNIVERSITY · PI GUAN, JIANJUN · 2016 to 2018
$1.1M
NHLBI NIH HHS R01 HL138175NHLBI NIH HHS R01 HL138353NHLBI NIH HHS R01 HL164062NHLBI NIH HHS R01 HL174055NIAMS NIH HHS R01 AR077616NIA NIH HHS R01 AG056919NIBIB NIH HHS R01 EB022018NIDDK NIH HHS R01 DK133949
6 · The paper itself

Abstract

Critical limb ischemia (CLI) leads to a high rate of limb amputation. Regenerating vasculature and skeletal muscles can save the affected limbs. Therapy using stem cell-derived extracellular vesicles (EVs) has emerged as a promising approach. However, the therapeutic efficacy is limited because EVs were not engineered to simultaneously possess the optimal composition of proangiogenic and promyogenic factors necessary to effectively support the survival, migration, and morphogenesis of endothelial and skeletal muscle cells under ischemic conditions. We discovered that the proangiogenic and promyogenic factors, including miR-126, miR-21, miR-296, miR-182, PDGF-BB, VEGF, bFGF, and HGF, can be concurrently upregulated in EVs derived from human iPSC-derived mesenchymal stem cells (iMSCs) by enhancing either N-cadherin-mediated or RGD-mediated interactions between the cells and matrix. Notably, enhancing N-cadherin interaction was more effective in upregulating these factors. The EVs from enhanced N-cadherin interaction markedly improved survival, migration, and morphogenesis of endothelial cells and myoblasts under the CLI-like conditions. To ensure targeted delivery to ischemic limbs, these EVs were cloaked with platelet membranes modified with an ischemia-homing peptide. Following intravenous delivery in a murine model of ischemic hindlimb, the EVs fully restored blood perfusion within 28 days, and significantly promoted skeletal muscle regeneration. These results underscore the potential of EVs with simultaneously upregulated proangiogenic and promyogenic factors in effectively treating CLI.

Indexed as

Extracellular VesiclesIschemiaMuscle, SkeletalNeovascularization, PhysiologicAnimalsCadherinsHindlimbHumansHuman Umbilical Vein Endothelial CellsInduced Pluripotent Stem CellsMaleMesenchymal Stem CellsMiceMice, Inbred C57BLMicroRNAsRegenerationCadherinsMicroRNAsAngiogenesisCritical limb ischemiaExtracellular vesiclesMuscle regenerationN-cadherin interaction

Identifiers

PMID40484285
PMCPMC12765455

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.