Evidence map›Paper›PMID 33403929›Full record

ArticleStem cells and development2021

Ultrafiltration and Injection of Islet Regenerative Stimuli Secreted by Pancreatic Mesenchymal Stromal Cells.

Tyler T Cooper, Stephen E Sherman, Gillian I Bell, Thamara Dayarathna, Danielle M McRae, Jun Ma, François Lagugné-Labarthet, Stephen H Pasternak, Gilles A Lajoie, David A Hess

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Stem cells and development, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
0.8field-weighted citation impact, top 30% 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

9 citing papers in PubMed, 14 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

10 authors at 2 institutions in 1 country.

Tyler T CooperDepartment of Physiology and Pharmacology, Western University, London, Canada.
Stephen E ShermanDepartment of Physiology and Pharmacology, Western University, London, Canada.
Gillian I BellMolecular Medicine Research Laboratories, Robarts Research Institute, London, Canada.
Thamara DayarathnaMolecular Medicine Research Laboratories, Robarts Research Institute, London, Canada.
Danielle M McRaeDepartment of Chemistry, Western University, London, Canada.
Jun MaMolecular Medicine Research Laboratories, Robarts Research Institute, London, Canada.
François Lagugné-LabarthetDepartment of Chemistry, Western University, London, Canada.
Stephen H PasternakMolecular Medicine Research Laboratories, Robarts Research Institute, London, Canada.
Gilles A LajoieDon Rix Protein Identification Facility, Department of Biochemistry and Western University, London, Canada.
David A HessDepartment of Physiology and Pharmacology, Western University, London, Canada.
Robarts Clinical Trials · CAWestern University · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The secretome of mesenchymal stromal cells (MSCs) is enriched for biotherapeutic effectors contained within and independent of extracellular vesicles (EVs) that may support tissue regeneration as an injectable agent. We have demonstrated that the intrapancreatic injection of concentrated conditioned media (CM) produced by bone marrow MSC supports islet regeneration and restored glycemic control in hyperglycemic mice, ultimately providing a platform to elucidate components of the MSC secretome. Herein, we extend these findings using human pancreas-derived MSC (Panc-MSC) as "biofactories" to enrich for tissue regenerative stimuli housed within distinct compartments of the secretome. Specifically, we utilized 100 kDa ultrafiltration as a simple method to debulk protein mass and to enrich for EVs while concentrating the MSC secretome into an injectable volume for preclinical assessments in murine models of blood vessel and islet regeneration. EV enrichment (EV+) was validated using nanoscale flow cytometry and atomic force microscopy, in addition to the detection of classical EV markers CD9, CD81, and CD63 using label-free mass spectrometry. EV+ CM was predominately enriched with mediators of wound healing and epithelial-to-mesenchymal transition that supported functional regeneration in mesenchymal and nonmesenchymal tissues. For example, EV+ CM supported human microvascular endothelial cell tubule formation in vitro and enhanced the recovery of blood perfusion following intramuscular injection in nonobese diabetic/severe combined immunodeficiency mice with unilateral hind limb ischemia. Furthermore, EV+ CM increased islet number and β cell mass, elevated circulating insulin, and improved glycemic control following intrapancreatic injection in streptozotocin-treated mice. Collectively, this study provides foundational evidence that Panc-MSC, readily propagated from the subculture of human islets, may be utilized for regenerative medicine applications.

Indexed as

AnimalsBiological FactorsBlood VesselsCells, CulturedCulture Media, ConditionedEndothelial CellsExtracellular VesiclesHumansHyperglycemiaMesenchymal Stem CellsMiceMice, Inbred NODMice, SCIDMicroscopy, Atomic ForcePancreasRegenerationBiological FactorsCulture Media, ConditionedStreptozocinextracellular vesiclesmesenchymal stromal cellspancreasproteomicsregenerative medicinetransplantation

Identifiers

PMID33403929
PMCPMC10331161
OpenAlexW3118563846

What OpenQuestion holds

Textmetadata
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.