Evidence map›Paper›PMID 33141458›Full record

ArticleStem cells (Dayton, Ohio)2021

Exosome-educated macrophages and exosomes differentially improve ligament healing.

Connie S Chamberlain, John A Kink, Linzie A Wildenauer, Maxwell McCaughey, Katie Henry, Andrea M Spiker, Matthew A Halanski, Peiman Hematti, Ray Vanderby

Open access · hybridAbstract read
In one paragraph

Article in Stem cells (Dayton, Ohio), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
43citing papers in PubMed, 1 pooled it
6.7field-weighted citation impact, top 2% of its field
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

43 citing papers in PubMed, 1 synthesis or guideline pooled it, 58 citations in OpenAlex.

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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

9 authors at 2 institutions in 1 country.

Connie S ChamberlainDepartment of Orthopedics and Rehabilitation, University of Wisconsin, Madison, Wisconsin, USA.ORCID 0000-0002-4980-4347
John A KinkDepartment of Medicine, University of Wisconsin, Madison, Wisconsin, USA.
Linzie A WildenauerDepartment of Orthopedics and Rehabilitation, University of Wisconsin, Madison, Wisconsin, USA.
Maxwell McCaugheyDepartment of Orthopedics and Rehabilitation, University of Wisconsin, Madison, Wisconsin, USA.
Katie HenryDepartment of Orthopedics and Rehabilitation, University of Wisconsin, Madison, Wisconsin, USA.
Andrea M SpikerDepartment of Orthopedics and Rehabilitation, University of Wisconsin, Madison, Wisconsin, USA.
Matthew A HalanskiDepartment of Orthopaedic Surgery and Rehabilitation, University of Nebraska Medical Center, Omaha, Nebraska, USA.
Peiman HemattiDepartment of Medicine, University of Wisconsin, Madison, Wisconsin, USA.
Ray VanderbyDepartment of Orthopedics and Rehabilitation, University of Wisconsin, Madison, Wisconsin, USA.
University of Wisconsin–Madison · USUniversity of Nebraska Medical Center · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Recently, our group used exosomes from mesenchymal stromal/stem cells (MSCs) to simulate an M2 macrophage phenotype, that is, exosome-educated macrophages (EEMs). These EEMs, when delivered in vivo, accelerated healing in a mouse Achilles tendon injury model. For the current study, we first tested the ability of EEMs to reproduce the beneficial healing effects in a different rodent model, that is, a rat medial collateral ligament (MCL) injury model. We hypothesized that treatment with EEMs would reduce inflammation and accelerate ligament healing, similar to our previous tendon results. Second, because of the translational advantages of a cell-free therapy, exosomes alone were also examined to promote MCL healing. We hypothesized that MSC-derived exosomes could also alter ligament healing to reduce scar formation. Similar to our previous Achilles tendon results, EEMs improved mechanical properties in the healing ligament and reduced inflammation, as indicated via a decreased endogenous M1/M2 macrophage ratio. We also showed that exosomes improved ligament remodeling as indicated by changes in collagen production and organization, and reduced scar formation but without improved mechanical behavior in healing tissue. Overall, our findings suggest EEMs and MSC-derived exosomes improve healing but via different mechanisms. EEMs and exosomes each have attractive characteristics as therapeutics. EEMs as a cell therapy are terminally differentiated and will not proliferate or differentiate. Alternatively, exosome therapy can be used as a cell free, shelf-stable therapeutic to deliver biologically active components. Results herein further support using EEMs and/or exosomes to improve ligament healing by modulating inflammation and promoting more advantageous tissue remodeling.

Indexed as

Achilles TendonAnimalsExosomesFemaleHeterograftsHumansMacrophagesMaleMesenchymal Stem CellsRatsRats, NudeRats, Wistarexosomesligament healingmacrophagesmesenchymal stromal cells

Identifiers

PMID33141458
PMCPMC7821004
OpenAlexW3096575601

What OpenQuestion 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 OpenQuestion graph.