Evidence map›Paper›PMID 35279175›Full record

ArticleImmunity & ageing : I & A2022

Ageing attenuates bone healing by mesenchymal stem cells in a microribbon hydrogel with a murine long bone critical-size defect model.

Hirohito Hirata, Ning Zhang, Masaya Ueno, Danial Barati, Junichi Kushioka, Huaishuang Shen, Masanori Tsubosaka, Masakazu Toya, Tzuhua Lin, Ejun Huang and 5 more

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

Article in Immunity & ageing : I & A, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed, 1 pooled it
3.1field-weighted citation impact, top 8% 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

12 citing papers in PubMed, 1 synthesis or guideline pooled it, 20 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

15 authors at 2 institutions in 3 countries.

Hirohito Hirata *Department of Orthopaedic Surgery, Stanford University, Stanford, California, USA.
Ning Zhang *Department of Orthopaedic Surgery, Stanford University, Stanford, California, USA.
Masaya UenoDepartment of Orthopaedic Surgery, Stanford University, Stanford, California, USA.
Danial BaratiDepartment of Orthopaedic Surgery, Stanford University, Stanford, California, USA.
Junichi KushiokaDepartment of Orthopaedic Surgery, Stanford University, Stanford, California, USA.
Huaishuang ShenDepartment of Orthopaedic Surgery, Stanford University, Stanford, California, USA.
Masanori TsubosakaDepartment of Orthopaedic Surgery, Stanford University, Stanford, California, USA.
Masakazu ToyaDepartment of Orthopaedic Surgery, Stanford University, Stanford, California, USA.
Tzuhua LinDepartment of Orthopaedic Surgery, Stanford University, Stanford, California, USA.
Ejun HuangDepartment of Orthopaedic Surgery, Stanford University, Stanford, California, USA.
Zhenyu YaoDepartment of Orthopaedic Surgery, Stanford University, Stanford, California, USA.
Joy Y WuDepartment of Medicine, Stanford University, Stanford, California, USA.
Stefan ZwingenbergerUniversity Center for Orthopaedics, Traumatology, and Plastic Surgery, University Hospital Carl Gustav Carus at Technische Universität Dresden, Dresden, Germany.
Fan YangDepartment of Orthopaedic Surgery, Stanford University, Stanford, California, USA.
Stuart B GoodmanDepartment of Orthopaedic Surgery, Stanford University, Stanford, California, USA. goodbone@stanford.edu.
Stanford University · USTU Dresden · DE

Funding

Customized MSCs to Enhance Healing of Bone DefectsR01AR073145 · NIAMS · STANFORD UNIVERSITY · PI GOODMAN, STUART B · 2018 to 2021
$1.4M
NIAMS NIH HHS R01AR073145Stanford University the Ellenburg Chair in Surgery
6 · The paper itself

Abstract

backgroundDespite the high incidence of fractures and pseudoarthrosis in the aged population, a potential role for the use of mesenchymal stem cells (MSCs) in the treatment of bone defects in elderly patients has not been elucidated. Inflammation and the innate immune system, including macrophages, play crucial roles in the differentiation and activation of MSCs. We have developed lentivirus-transduced interleukin 4 (IL4) over-expressing MSCs (IL4-MSCs) to polarize macrophages to an M2 phenotype to promote bone healing in an established young murine critical size bone defect model. In the current study, we explore the potential of IL4-MSCs in aged mice.

methodsA 2 mm femoral diaphyseal bone defect was created and fixed with an external fixation device in 15- to 17-month-old male and female BALB/c mice. Microribbon (µRB) scaffolds (Sc) with or without encapsulation of MSCs were implanted in the defect sites. Accordingly, the mice were divided into three treatment groups: Sc-only, Sc + MSCs, and Sc + IL4-MSCs. Mice were euthanized six weeks after the surgery; subsequently, MicroCT (µCT), histochemical and immunohistochemical analyses were performed.

resultsµCT analysis revealed that bone formation was markedly enhanced in the IL4-MSC group. Compared with the Sc-only, the amount of new bone increased in the Sc + MSCs and Sc + IL4-MSC groups. However, no bridging of bone was observed in all groups. H&E staining showed fibrous tissue within the defect in all groups. Alkaline phosphatase (ALP) staining was increased in the Sc + IL4-MSC group. The Sc + IL4-MSCs group showed a decrease in the number of M1 macrophages and an increase in the number of M2 macrophages, with a significant increase in the M2/M1 ratio. DISCUSSION: IL4 promotes macrophage polarization to an M2 phenotype, facilitating osteogenesis and vasculogenesis. The addition of IL4-MSCs in the µRB scaffold polarized macrophages to an M2 phenotype and increased bone formation; however, complete bone bridging was not observed in any specimens. These results suggest that IL4-MSCs are insufficient to heal a critical size bone defect in aged mice, as opposed to younger animals. Additional therapeutic strategies are needed in this challenging clinical scenario.

Indexed as

AgeingBone healinginterleukin-4Mesenchymal stem cellMicroribbon hydrogel

Identifiers

PMID35279175
PMCPMC8917642
OpenAlexW4220656848

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.