Evidence map›Paper›PMID 39402677›Full record

ArticleStem cell research & therapy2024

iPSC-derived megakaryocytes and platelets accelerate wound healing and angiogenesis.

Kentaro Kosaka, Naoya Takayama, Sudip Kumar Paul, Maria Alejandra Kanashiro, Motohiko Oshima, Masaki Fukuyo, Bahityar Rahmutulla, Ikuko Tajiri, Michiaki Mukai, Yoshitaka Kubota and 6 more

Abstract read
In one paragraph

Article in Stem cell research & therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

6 citing papers in PubMed.

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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

16 authors.

Kentaro KosakaDepartment of Plastic, Reconstructive, and Aesthetic Surgery, Chiba University Graduate School of Medicine, Chiba, Japan. knt.k-6098@hotmail.co.jp.ORCID 0009-0002-6858-9870
Naoya TakayamaDepartment of Regenerative Medicine, Chiba University Graduate School of Medicine, Chiba, Japan.
Sudip Kumar PaulDepartment of Regenerative Medicine, Chiba University Graduate School of Medicine, Chiba, Japan.
Maria Alejandra KanashiroDepartment of Regenerative Medicine, Chiba University Graduate School of Medicine, Chiba, Japan.
Motohiko OshimaDivision of Stem Cell and Molecular Medicine, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Masaki FukuyoDepartment of Molecular Oncology, Chiba University Graduate School of Medicine, Chiba, Japan.
Bahityar RahmutullaDepartment of Molecular Oncology, Chiba University Graduate School of Medicine, Chiba, Japan.
Ikuko TajiriDepartment of Orthopedic Surgery, Chiba University Graduate School of Medicine, Chiba, Japan.
Michiaki MukaiDepartment of Orthopedic Surgery, Chiba University Graduate School of Medicine, Chiba, Japan.
Yoshitaka KubotaDepartment of Plastic, Reconstructive, and Aesthetic Surgery, Chiba University Graduate School of Medicine, Chiba, Japan.
Shinsuke AkitaDepartment of Plastic, Reconstructive, and Aesthetic Surgery, Chiba University Graduate School of Medicine, Chiba, Japan.
Nobutaka FuruyamaJiyugaoka Clinic, Tokyo, Japan.
Atsushi KanedaDepartment of Molecular Oncology, Chiba University Graduate School of Medicine, Chiba, Japan.
Atsushi IwamaDivision of Stem Cell and Molecular Medicine, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Koji EtoDepartment of Regenerative Medicine, Chiba University Graduate School of Medicine, Chiba, Japan. kojieto@cira.kyoto-u.ac.jp.
Nobuyuki MitsukawaDepartment of Plastic, Reconstructive, and Aesthetic Surgery, Chiba University Graduate School of Medicine, Chiba, Japan. nmitsu@faculty.chiba-u.jp.

Funding

Incubation Program of Kyoto University Incubation Program of Kyoto UniversityJapan Society for the Promotion of Science 21H05047SJapan Society for the Promotion of Science JP21K16921Japan Society for the Promotion of Science JP23K09095Jiyugaoka Clinic Doctor's Cosmetics Jiyugaoka Clinic Doctor's CosmeticsSBC Medical Promotion Foundation SBC Medical Promotion FoundationShin-kuki General Hospital Shin-kuki General HospitalShin-yurigaoka General Hospital Shin-yurigaoka General HospitalTerumo Life Science Foundation 19-II401
6 · The paper itself

Abstract

backgroundPlatelet-rich plasma (PRP), which is prepared by concentrating platelets in autologous blood, shows efficacy in chronic skin wounds via multiple growth factors. However, it exhibits heterogeneity across patients, leading to unstable therapeutic efficacy. Human induced pluripotent stem cell (iPSC)-derived megakaryocytes and platelets (iMPs) are capable of providing a stable supply, holding promise as materials for novel platelet concentrate-based therapies. In this context, we evaluated the effect of iMPs on wound healing and validated lyophilization for clinical applications.

methodsThe growth factors released by activated iMPs were measured. The effect of the administration of iMPs on human fibroblasts and human umbilical vein endothelial cells (HUVECs) was investigated in vitro. iMPs were applied to dorsal skin defects of diabetic mice to assess the wound closure rate and quantify collagen deposition and angiogenesis. Following the storage of freeze-dried iMPs (FD-iMPs) for three months, the stability of growth factors and their efficacy in animal models were determined.

resultMultiple growth factors that promote wound healing were detected in activated iMPs. iMPs specifically released FGF2 and exhibited a superior enhancement of HUVEC proliferation compared to PRP. Moreover, an RNA-seq analysis revealed that iMPs induce polarization to stalk cells and enhance ANGPTL4 gene expression in HUVECs. Animal studies demonstrated that iMPs promoted wound closure and angiogenesis in chronic wounds caused by diabetes. We also confirmed the long-term stability of growth factors in FD-iMPs and their comparable effects to those of original iMPs in the animal model.

conclusionOur study demonstrates that iMPs promote angiogenesis and wound healing through the activation of vascular endothelial cells. iMPs exhibited more effectiveness than PRP, an effect attributed to the exclusive presence of specific factors including FGF2. Lyophilization enabled the long-term maintenance of the composition of the growth factors and efficacy of the iMPs, therefore contributing to stable supply for clinical application. These findings suggest that iMPs provide a novel treatment for chronic wounds.

Indexed as

Blood PlateletsInduced Pluripotent Stem CellsMegakaryocytesNeovascularization, PhysiologicWound HealingAngiogenesisAnimalsDiabetes Mellitus, ExperimentalHumansHuman Umbilical Vein Endothelial CellsMiceGrowth factorsImmortalized megakaryocyte cell linesLyophilizationPlateletsWound healing

Identifiers

PMID39402677
PMCPMC11477011

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LicenceCC BY-NC-ND
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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.