Evidence map›Paper›PMID 42751092›Full record

ArticleMaterials today. Bio2026

Stage-specific MSC spheroid fusion enables bottom-up formation of stage-defined hierarchical cartilage graft.

Yen-Liang Liu, Yun-Chieh Lin, Yi-Chen Tsai, Chun-Che Yen, Chun-Yi Chiang, Pen-Jung Hung, Yu-Ting Huang, Chih-Hung Chang, Feng-Huei Lin, Hwa-Chang Liu

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Article in Materials today. Bio, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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1 · What the graph read from it

What it found

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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

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

10 authors.

Yen-Liang LiuMaster Program for Biomedical Engineering, College of Biomedical Engineering, China Medical University, Taichung City, 406040, Taiwan.
Yun-Chieh LinDepartment of Orthopaedic Surgery, National Taiwan University Hospital, Taipei City, 100225, Taiwan.
Yi-Chen TsaiDepartment of Biomedical Engineering, College of Biomedical Engineering, China Medical University, Taichung City, 406040, Taiwan.
Chun-Che YenKartigen Biomedical Inc., Taipei City, 100047, Taiwan.
Chun-Yi ChiangPh.D. Program for Aging, College of Medicine, China Medical University, Taichung City, 406040, Taiwan.
Pen-Jung HungCancer Biology and Precision Therapeutics Center, China Medical University, Taichung City, 406040, Taiwan.
Yu-Ting HuangMaster Program for Biomedical Engineering, College of Biomedical Engineering, China Medical University, Taichung City, 406040, Taiwan.
Chih-Hung ChangDepartment of Orthopaedic Surgery, Far Eastern Memorial Hospital, New Taipei City, 220216, Taiwan.
Feng-Huei LinPh.D. Program for Aging, College of Medicine, China Medical University, Taichung City, 406040, Taiwan.
Hwa-Chang LiuDepartment of Orthopaedic Surgery, National Taiwan University Hospital, Taipei City, 100225, Taiwan.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Engineering articular cartilage with hierarchical architecture and effective interfacial integration remains a major challenge. Although bottom-up spheroid assembly offers a promising biofabrication strategy, how chondrogenic maturation influences spheroid fusion and boundary remodeling remains incompletely defined. Here, we investigated differentiation stage as a programmable determinant of the phenotype and assembly behavior of mesenchymal stem cell (MSC)-derived chondrogenic spheroids. Exploratory RNA-seq pathway mapping, complemented by biologically replicated RT-qPCR, indicated stage- and cell-source-associated differences in cartilage matrix and maturation-related programs in bone marrow-derived MSCs (BM-MSCs) and umbilical cord-derived MSCs (UC-MSCs). Early-stage spheroids exhibited greater fusion capacity than mature spheroids, whereas incorporation of undifferentiated MSCs promoted the integration of mature chondrogenic spheroids and reduced persistent inter-spheroid boundaries. Sequential assembly of Day-3, Day-7, and Day-14 spheroids generated hierarchical constructs with stage-associated regional differences in cartilage extracellular matrix deposition. Incorporating an undifferentiated MSC layer at the bone-facing interface further supported structural continuity with a porous bone substitute in vitro. In an exploratory porcine pilot study involving two animals, implantation of MSC-derived spheroid grafts into cartilage defects was technically feasible. At 6 months, the repair tissue exhibited variable proteoglycan staining and heterogeneous collagen type II immunoreactivity, while selected sections showed tissue apposition at the graft-host interface. The limited animal-level sample size precluded conclusions regarding repair efficacy, cartilage quality, or superiority over autologous cartilage implantation. Collectively, these findings identify differentiation stage as an intrinsic bioassembly variable and establish a stage-programmed strategy for constructing hierarchical cartilage grafts. Both BM-MSCs and UC-MSCs supported stage-defined assembly in vitro, warranting further evaluation of UC-MSCs as a potential allogeneic cell source in adequately powered studies.

Indexed as

Bone marrow mesenchymal stem cellCartilage defectChondrocyte-precursorSpheroidUmbilical cord mesenchymal stem cell

Identifiers

PMID42751092
PMCPMC13579038

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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.