Evidence map›Paper›PMID 32945622›Full record

ArticleStem cells translational medicine2021

Overexpression of alpha-1 antitrypsin in mesenchymal stromal cells improves their intrinsic biological properties and therapeutic effects in nonobese diabetic mice.

Lili Song, Wenyu Gou, Jingjing Wang, Hua Wei, Jennifer Lee, Charlie Strange, Hongjun Wang

Open access · goldAbstract read
In one paragraph

Article in Stem cells translational medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
1.9field-weighted citation impact, top 13% 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

16 citing papers in PubMed, 25 citations in OpenAlex.

  1. Article
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  4. AAT-MSC-EVs: Novel implications for suppressing ferroptosis, fibrosis and pain associated with chronic pancreatitis.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
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  15. A preview of selected articles.Stem cells translational medicine · 2021
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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

7 authors at 1 institution in 1 country.

Lili SongDepartment of Surgery, Medical University of South Carolina, Charleston, South Carolina, USA.
Wenyu GouDepartment of Surgery, Medical University of South Carolina, Charleston, South Carolina, USA.
Jingjing WangDepartment of Surgery, Medical University of South Carolina, Charleston, South Carolina, USA.
Hua WeiDepartment of Surgery, Medical University of South Carolina, Charleston, South Carolina, USA.
Jennifer LeeAcademic Magnet High School, North Charleston, South Carolina, USA.
Charlie StrangeDepartment of Medicine, Medical University of South Carolina, Charleston, South Carolina, USA.
Hongjun WangDepartment of Surgery, Medical University of South Carolina, Charleston, South Carolina, USA.ORCID 0000-0001-7421-1917
Medical University of South Carolina · US

Funding

Proteomics CoreP30DK123704 · NIDDK · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI DON C. ROCKEY · 2020 to 2026
$8.8M
Cellular Therapy for Type 1 Diabetes using Mesenchymal Stem CellsR01DK118529 · NIDDK · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI WANG, HONGJUN · 2019 to 2025
$3.8M
Autologous BM-MSCs and Islet Co-transplantation to Enhance Islet Survival and Function in TP-IAT PatientsR01DK126454 · NIDDK · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI WANG, HONGJUN · 2021 to 2025
$3.2M
Novel Gene and Stem Cell Therapy for Type 1 DiabetesR01DK120394 · NIDDK · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI WANG, HONGJUN · 2018 to 2021
$2.2M
Alpha1 Anti-trypsin Enhances Islet Autograft SurvivalR01DK105183 · NIDDK · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI WANG, HONGJUN · 2016 to 2020
$2.0M
hAAT-engineered Mesenchymal Stem Cells for the Treatment of Chronic PainI01BX004536 · VA · RALPH H JOHNSON VA MEDICAL CENTER · PI Hongjun Wang · 2020 to 2026
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BLRD VA I01 BX004536NIDDK NIH HHS P30 DK123704NIDDK NIH HHS R01 DK105183NIDDK NIH HHS R01 DK118529NIDDK NIH HHS R01 DK120394NIDDK NIH HHS R01 DK126454
6 · The paper itself

Abstract

Islet/β cell dysfunction and death caused by autoimmune-mediated injuries are major features of type 1 diabetes (T1D). Mesenchymal stromal cells (MSCs) have been used for the treatment of T1D in animal models and clinical trials. Based on the anti-inflammatory effects of alpha-1 antitrypsin (AAT), we generated human AAT engineered MSCs (hAAT-MSCs) by infecting human bone marrow-derived MSCs with the pHAGE CMV-a1aT-UBC-GFP-W lentiviral vector. We compared the colony forming, differentiation, and migration capacity of empty virus-treated MSCs (hMSC) and hAAT-MSCs and tested their protective effects in the prevention of onset of T1D in nonobese diabetic (NOD) mice. hAAT-MSCs showed increased self-renewal, better migration and multilineage differentiation abilities compared to hMSCs. In addition, polymerase chain reaction array for 84 MSC-related genes showed that 23 genes were upregulated, and 3 genes were downregulated in hAAT-MSCs compared to hMSCs. Upregulated genes include those critical for the stemness (ie, Wnt family member 3A [WNT3A], kinase insert domain receptor [KDR]), migration (intercellular adhesion molecule 1 [ICAM-1], vascular cell adhesion protein 1 [VICAM-1], matrix metalloproteinase-2 [MMP2]), and survival (insulin-like growth factor 1 [IGF-1]) of MSCs. Pathway analysis showed that changed genes were related to growth factor activity, positive regulation of cell migration, and positive regulation of transcription. In vivo, a single intravenous infusion of hAAT-MSCs significantly limited inflammatory infiltration into islets and delayed diabetes onset in the NOD mice compared with those receiving vehicle or hMSCs. Taken together, overexpression of hAAT in MSCs improved intrinsic biological properties of MSCs needed for cellular therapy for the treatment of T1D.

Indexed as

alpha 1-AntitrypsinDiabetes Mellitus, ExperimentalDiabetes Mellitus, Type 1Mesenchymal Stem Cell TransplantationAnimalsMatrix Metalloproteinase 2Mesenchymal Stem CellsMiceMice, Inbred NODalpha 1-AntitrypsinMatrix Metalloproteinase 2diabetes onsethuman α-1 antitrypsinmesenchymal stromal cellsstemnesstype 1 diabetes

Identifiers

PMID32945622
PMCPMC7848369
OpenAlexW3087098435

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.