Evidence map›Paper›PMID 42256838›Full record

ReviewClinical, cosmetic and investigational dentistry2026

Regenerative Potential of Exosomes from 3D Spheroid-Cultured Stem Cells Compared with 2D Culture in Dentin-Pulp Regeneration: A Systematic Review.

Hesti Witasari Jos Erry, Anggraini Margono, Dini Asrianti Bagio, Dewi Fatma Suniarti, Indra Kusuma, Hendrik Setia Budi, Rachmat Mauludin, Rahmi Syaflida Dalimunthe, Dodi Valentino Tambun, Lisa Rinanda Amir

Abstract readReview
In one paragraph

Review in Clinical, cosmetic and investigational dentistry, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

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

10 authors.

Hesti Witasari Jos ErryFaculty of Dentistry, Universitas Indonesia, Jakarta, Indonesia.
Anggraini MargonoFaculty of Dentistry, Universitas Indonesia, Jakarta, Indonesia.
Dini Asrianti BagioFaculty of Dentistry, Universitas Indonesia, Jakarta, Indonesia.ORCID 0000-0001-7176-724X
Dewi Fatma SuniartiFaculty of Dentistry, Universitas Indonesia, Jakarta, Indonesia.
Indra KusumaFaculty of Medicine, Universitas YARSI, Jakarta, Indonesia.ORCID 0000-0002-7689-451X
Hendrik Setia BudiFaculty of Dentistry, Universitas Airlangga, Surabaya, Indonesia.ORCID 0000-0002-5518-3372
Rachmat MauludinSchool of Pharmacy, Institut Teknologi Bandung, Bandung, Indonesia.
Rahmi Syaflida DalimuntheFaculty of Dentistry, Universitas Indonesia, Jakarta, Indonesia.
Dodi Valentino TambunFaculty of Dentistry, Universitas Indonesia, Jakarta, Indonesia.
Lisa Rinanda AmirFaculty of Dentistry, Universitas Indonesia, Jakarta, Indonesia.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Purpose: This systematic review aimed to evaluate the current preclinical evidence on exosomes derived from three-dimensional stem cell culture systems and their direct or indirect relevance to dentin-pulp regeneration. Exosomes derived from stem cells have emerged as promising mediators of tissue regeneration because of their ability to transfer bioactive molecules that regulate cellular communication and tissue repair. Recent studies suggest that exosomes obtained from three-dimensional (3D) spheroid cultures may exhibit enhanced regenerative properties compared with those derived from conventional two-dimensional cultures. Methods: A systematic review was conducted following the PRISMA 2020 guidelines. Electronic searches were performed in PubMed, Scopus, and ProQuest databases to identify relevant studies investigating exosomes derived from 3D cell culture systems with potential relevance to dentin-pulp regeneration. Studies were screened according to predefined inclusion and exclusion criteria. Data extraction focused on cell sources, exosome isolation methods, characterization techniques, and biological effects related to dental pulp regeneration. Results: Ten studies met the inclusion criteria. The included studies demonstrated that exosomes derived from 3D spheroid cultures may enhance angiogenesis, support odontogenic differentiation, reduce inflammatory responses, and promote regenerative tissue repair. Several studies also reported increased expression of regenerative markers and improved cellular proliferation when compared with exosomes derived from conventional two-dimensional cultures. However, only a limited number of studies directly investigated dentin-pulp-related outcomes, while several provided indirect mechanistic evidence from non-dental preclinical models. Conclusion: Exosomes derived from three-dimensional culture systems show promising potential as a cell-free therapeutic strategy for dentin-pulp regeneration. These vesicles may improve tissue repair through enhanced biological activity. However, the current evidence remains mainly preclinical, heterogeneous, and partly indirect. Further standardized experimental studies and clinical investigations are required to validate their translational application in regenerative endodontic therapy.

Indexed as

dental pulp stem cellsdentin–pulp regenerationexosomesextracellular vesiclesregenerative endodonticsthree-dimensional culture

Identifiers

PMID42256838
PMCPMC13242206

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.