Evidence map›Paper›PMID 32537359›Full record

ArticlePlastic and reconstructive surgery. Global open2020

Therapeutic Reversal of Radiotherapy Injury to Pro-fibrotic Dysfunctional Fibroblasts In Vitro Using Adipose-derived Stem Cells.

Lipi Shukla, Rodney Luwor, Matthew E Ritchie, Shiva Akbarzadeh, Hong-Jian Zhu, Wayne Morrison, Tara Karnezis, Ramin Shayan

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

Article in Plastic and reconstructive surgery. Global open, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed, 1 pooled it
0.8field-weighted citation impact, top 29% 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

5 citing papers in PubMed, 1 synthesis or guideline pooled it, 11 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Review
  5. Review
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

8 authors at 6 institutions in 1 country.

Lipi ShuklaRegenerative Surgery and Lymphatics Department, O'Brien Institute, St. Vincent's Institute, Fitzroy, Victoria, Australia.
Rodney LuworDepartment of Surgery, The University of Melbourne, The Royal Melbourne Hospital, Victoria, Australia.
Matthew E RitchieEpigenetics and Development Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
Shiva AkbarzadehSkin Bioengineering Laboratory, Victorian Adult Burns Service, The Alfred Hospital, Victoria, Australia.
Hong-Jian ZhuDepartment of Surgery, The University of Melbourne, The Royal Melbourne Hospital, Victoria, Australia.
Wayne MorrisonRegenerative Surgery and Lymphatics Department, O'Brien Institute, St. Vincent's Institute, Fitzroy, Victoria, Australia.
Tara KarnezisRegenerative Surgery and Lymphatics Department, O'Brien Institute, St. Vincent's Institute, Fitzroy, Victoria, Australia.
Ramin ShayanRegenerative Surgery and Lymphatics Department, O'Brien Institute, St. Vincent's Institute, Fitzroy, Victoria, Australia.
St Vincent's Hospital · AUUniversity of Melbourne · AUAustralian Catholic University · AUO'Brien Institute · AUThe Alfred Hospital · AUWalter and Eliza Hall Institute of Medical Research · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Cancer patients often require radiotherapy (RTx) to enhance their survival. Unfortunately, RTx also damages nearby healthy non-cancer tissues, leading to progressive fibrotic soft-tissue injury, consisting of pain, contracture, tissue-breakdown, infection, and lymphoedema. Mechanisms underlying the clinically observed ability of fat grafting to ameliorate some of these effects, however, are poorly understood. It was hypothesized that RTx significantly alters fibroblast cell function and the paracrine secretome of adipose-derived stem cells (ADSC) may mitigate these changes.

methodsTo investigate cellular changes resulting in the fibrotic side-effects of RTx, cultured normal human dermal fibroblasts (NHDF) were irradiated (10Gy), then studied using functional assays that reflect key fibroblast functions, and compared with unirradiated controls. RNA-Seq and targeted microarrays (with specific examination of TGFβ) were performed to elucidate altered gene pathways. Finally, conditioned-media from ADSC was used to treat irradiated fibroblasts and model fat graft surgery.

resultsRTx altered NHDF morphology, with cellular functional changes reflecting transition into a more invasive phenotype: increased migration, adhesion, contractility, and disordered invasion. Changes in genes regulating collagen and MMP homeostasis and cell-cycle progression were also detected. However, TGFβ was not identified as a key intracellular regulator of the fibroblast response. Finally, treatment with ADSC-conditioned media reversed the RTx-induced hypermigratory state of NHDF.

conclusionsOur findings regarding cellular and molecular changes in irradiated fibroblasts help explain clinical manifestations of debilitating RTx-induced fibrosis. ADSC-secretome-mediated reversal indicated that these constituents may be used to combat the devastating side-effects of excessive unwanted fibrosis in RTx and other human fibrotic diseases.

Identifiers

PMID32537359
PMCPMC7253248
OpenAlexW3013354946

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.