Evidence map›Paper›PMID 38072920›Full record

ArticleStem cell research & therapy2023

Umbilical cord-derived mesenchymal stem cell sheets transplanted subcutaneously enhance cell retention and survival more than dissociated stem cell injections.

Mitsuyoshi Nakao, Makoto Matsui, Kyungsook Kim, Nobuhiro Nishiyama, David W Grainger, Teruo Okano, Hideko Kanazawa, Kenichi Nagase

Abstract read
In one paragraph

Article in Stem cell research & therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
–field-weighted citation impact
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. Article
  2. Article
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  4. Article
  5. Review
  6. Temperature-modulated separation of therapeutic cells, viral vectors, and exosomes using functional polymers.Analytical sciences : the international journal of the Japan Society for Analytical Chemistry · 2025
    Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Bioanalytical technologies using temperature-responsive polymers.Analytical sciences : the international journal of the Japan Society for Analytical Chemistry · 2024
    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.

Mitsuyoshi NakaoFaculty of Pharmacy, Keio University, 1-5-30 Shibakoen, Minato-ku, Tokyo, 105-8512, Japan.
Makoto MatsuiLaboratory for Chemistry and Life Science, Institute of Innovative Research, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama, Kanagawa, 226-8503, Japan.
Kyungsook KimCell Sheet Tissue Engineering Center (CSTEC), Department of Molecular Pharmaceutics, University of Utah, Health Sciences, Salt Lake City, UT, 84112, USA.
Nobuhiro NishiyamaLaboratory for Chemistry and Life Science, Institute of Innovative Research, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama, Kanagawa, 226-8503, Japan.
David W GraingerCell Sheet Tissue Engineering Center (CSTEC), Department of Molecular Pharmaceutics, University of Utah, Health Sciences, Salt Lake City, UT, 84112, USA.
Teruo OkanoCell Sheet Tissue Engineering Center (CSTEC), Department of Molecular Pharmaceutics, University of Utah, Health Sciences, Salt Lake City, UT, 84112, USA.
Hideko KanazawaFaculty of Pharmacy, Keio University, 1-5-30 Shibakoen, Minato-ku, Tokyo, 105-8512, Japan.
Kenichi NagaseFaculty of Pharmacy, Keio University, 1-5-30 Shibakoen, Minato-ku, Tokyo, 105-8512, Japan. nagase-kn@pha.keio.ac.jp.ORCID 0000-0002-6575-0107

Funding

Japan Society for the Promotion of Science 18K19938Japan Society for the Promotion of Science 19H02447Japan Society for the Promotion of Science 20H05233Japan Society for the Promotion of Science 21KK0199Japan Society for the Promotion of Science 22H04560Japan Society for the Promotion of Science 22K19899
6 · The paper itself

Abstract

backgroundHuman umbilical cord-derived mesenchymal stem cell (hUC-MSC) sheets have recently attracted attention as an alternative approach to injected cell suspensions for stem cell therapy. However, cell engraftment and cytokine expression levels between hUC-MSC sheets and their cell suspensions in vivo have not yet been compared. This study compares hUC-MSC in vivo engraftment efficacy and cytokine expression for both hUC-MSC sheets and cell suspensions.

methodshUC-MSC sheets were prepared using temperature-responsive cell culture; two types of hUC-MSC suspensions were prepared, either by enzymatic treatment (trypsin) or by enzyme-free temperature reduction using temperature-responsive cell cultureware. hUC-MSC sheets and suspensions were transplanted subcutaneously into ICR mice through subcutaneous surgical placement and intravenous injection, respectively. hUC-MSC sheet engraftment after subcutaneous surgical transplantation was investigated by in vivo imaging while intravenously injected cell suspensions were analyzing using in vitro organ imaging. Cytokine levels in both transplant site tissues and blood were quantified by enzyme-linked immunosorbent assay.

resultsAfter subcutaneous transplant, hUC-MSC sheets exhibited longer engraftment duration than hUC-MSC suspensions. This was attributed to extracellular matrix (ECM) and cell-cell junctions retained in sheets but enzymatically altered in suspensions. hUC-MSC suspensions harvested using enzyme-free temperature reduction exhibited relatively long engraftment duration after intravenous injection compared to suspensions prepared using trypsin, as enzyme-free harvest preserved cellular ECM. High HGF and TGF-β1 levels were observed in sheet-transplanted sites compared to hUC-MSC suspension sites. However, no differences in human cytokine levels in murine blood were detected, indicating that hUC-MSC sheets might exert local paracrine rather than endocrine effects.

conclusionshUC-MSC sheet transplantation could be a more effective cell therapeutic approach due to enhanced engraftment and secretion of therapeutic cytokines over injected hUC-MSC suspensions.

Indexed as

Mesenchymal Stem CellsMesenchymal Stem Cell TransplantationAnimalsCytokinesHumansMiceMice, Inbred ICRTrypsinUmbilical CordCytokinesTrypsinCell retentionCell sheet transplantationCytokine expressionEngraftmentTemperature-responsive cell cultureware

Identifiers

PMID38072920
PMCPMC10712142

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Registered trials

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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.