Evidence map›Paper›PMID 41259786›Full record

ArticleStem cells translational medicine2025

Teratoma-free cartilage regeneration using p21-/- iPSCs engineered with iCasp9.

Leila Larijani, Derrick Rancourt, Roman J Krawetz

Abstract read
In one paragraph

Article in Stem cells translational medicine, 2025. 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

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

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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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

3 authors.

Leila LarijaniMcCaig Institute for Bone & Joint Health, University of Calgary, Calgary, Alberta T2N4N1Canada.
Derrick RancourtMcCaig Institute for Bone & Joint Health, University of Calgary, Calgary, Alberta T2N4N1Canada.
Roman J KrawetzMcCaig Institute for Bone & Joint Health, University of Calgary, Calgary, Alberta T2N4N1Canada.ORCID 0000-0002-2576-4504

Funding

Canada Foundation for InnovationCanadian Institutes for Health Research 201309MOP-311542-DIB-CBBA-170939
6 · The paper itself

Abstract

objectiveArticular cartilage has limited regenerative capacity due to its lack of innervation, vascularization, and lymphatic vessels. As cartilage is devoid of nerves, injuries often go unnoticed until degeneration leads to pain, reduced function, and ultimately osteoarthritis (OA). Treatment options for cartilage injury, both surgical and nonsurgical, depend on factors like defect size, shape, depth, location, and patient age. Stem cells, particularly their ability to differentiate into chondrocytes, hold promise for cartilage repair, but no therapies have yet gained clinical approval. Recently, induced pluripotent stem cells (iPSCs) have emerged as a potential solution for cartilage regeneration. However, post-transplantation tumorigenesis remains a significant concern. To mitigate this risk, robust quality and safety protocols are needed, alongside safety mechanisms to control iPSC behavior after transplantation.

designThe iCaspase9 (iCasp9) cell suicide system offers a promising solution, enabling selective elimination of genetically modified cells via apoptosis. We previously demonstrated that the efficiency of iCasp9-mediated killing increases in a p21 mutant background. Since p21 mutations also enhance cartilage repair, we investigated iCasp9-engineered p21-/- and wildtype (p21+/+) iPSCs in a mouse cartilage injury model.

resultsWithout iCasp9 activation, both p21-/- and p21+/+ iPSCs formed tumors post-transplantation. In contrast, mice treated with the iCasp9 activator AP20187 showed no tumors. Both p21-/- and p21+/+ iPSCs demonstrated similar cartilage regeneration.

conclusionsThese findings suggest that iCasp9-mediated elimination of iPSCs can effectively mitigate tumor risks while preserving their therapeutic potential for cartilage repair.

Indexed as

Cartilage, ArticularCyclin-Dependent Kinase Inhibitor p21Induced Pluripotent Stem CellsRegenerationAnimalsHumansMiceTeratomaCyclin-Dependent Kinase Inhibitor p21cartilage regenerationiCasp9induced pluripotent stem cellstumor formation

Identifiers

PMID41259786
PMCPMC12629534

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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.