Evidence map›Paper›PMID 42543249›Full record

ReviewBioMed research international2026

Cell-Free Fat Extract (CEFFE) as a Versatile Cell-Free Biologic for Multitissue Regeneration: From Skin and Bone to Nerve, Reproductive, and Systemic Applications-A Comprehensive Review.

Arian Karimi Rouzbahani, Mahya Aliakbari, Bahar Amiri, Tahereh Fereydoonnezhad, Arya Behzadi, Somayeh Delfani, Zeinab Sharafi, Sepehr Miran, Abdolrazagh Marzban

Abstract readReview
In one paragraph

Review in BioMed research international, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

9 authors.

Arian Karimi RouzbahaniRazi Herbal Medicines Research Center, Lorestan University of Medical Sciences, Khorramabad, Iran, lums.ac.ir.ORCID https://orcid.org/0000-0002-0239-503X
Mahya AliakbariStudent Research Committee, School of Medicine, Bushehr University of Medical Sciences, Bushehr, Iran, bpums.ac.ir.
Bahar AmiriStudent Research Committee, Lorestan University of Medical Sciences, Khorramabad, Iran, lums.ac.ir.ORCID https://orcid.org/0009-0008-1842-1520
Tahereh FereydoonnezhadStudent Research Committee, Bushehr University of Medical Sciences, Bushehr, Iran, bpums.ac.ir.
Arya BehzadiSurgery Education and Researching Network (SERGN), Universal Scientific Education and Research Network (USERN), Melbourne, Australia, usern.tums.ac.ir.ORCID https://orcid.org/0000-0002-9927-8891
Somayeh DelfaniDepartment of Biochemistry, School of Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran, lums.ac.ir.
Zeinab SharafiRazi Herbal Medicines Research Center, Lorestan University of Medical Sciences, Khorramabad, Iran, lums.ac.ir.
Sepehr MiranAlfred Health, Department of Urology, Melbourne, Australia, alfred.org.au.ORCID https://orcid.org/0009-0008-5938-1094
Abdolrazagh MarzbanRazi Herbal Medicines Research Center, Lorestan University of Medical Sciences, Khorramabad, Iran, lums.ac.ir.ORCID https://orcid.org/0000-0002-2027-8910

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundCell-free fat extract (CEFFE), an adipose-derived biologic, offers a potent alternative to cell-based therapies by delivering a complex milieu of growth factors (e.g., VEGF, EGF, and BDNF) and regulatory proteins without the tumorigenic, immunogenic, or ethical challenges associated with stem cell applications.

objectiveThe objective of this study is to systematically evaluate CEFFE's regenerative efficacy across diverse tissue systems-including musculoskeletal, neural, reproductive, dermal, ocular, and systemic applications-while synthesizing its underlying molecular mechanisms, clinical outcomes, and translational challenges.

methodsA comprehensive literature review was conducted utilizing databases such as PubMed, Scopus, and Web of Science, focusing on preclinical and clinical studies published from January 2018 to May 2026. Over 55 articles were analyzed to evaluate CEFFE's efficacy, dosage-response patterns, and molecular pathways.

resultsCEFFE accelerates tissue repair through three conserved mechanistic axes: antiapoptotic survival (e.g., PI3K-Akt/mTOR activation and NRF2-mediated antiferroptosis), context-specific immunomodulation (e.g., Annexin A5-mediated M2 macrophage polarization and NLRP3 inflammasome disruption), and extracellular matrix remodeling alongside angiogenesis (e.g., TGF-β/Smad signaling). Emerging evidence highlights CEFFE's efficacy in novel domains such as intervertebral disc degeneration, corneal neurodegeneration, systemic sepsis, and as an IVF culture media supplement. Clinical trials confirm its safety and efficacy in dermatological applications (e.g., infraorbital aging and hyperpigmentation) and demonstrate superiority over standard treatments, such as hyaluronic acid, for early-to-mid-stage osteoarthritis.

conclusionsCEFFE represents a highly versatile and precise cell-free biologic capable of driving multitissue regeneration. To fully realize its clinical and commercial potential, future research must address donor variability by establishing standardized dosing protocols, implementing key-molecule quantification for batch consistency, and conducting large-scale, multicenter randomized controlled trials.

Indexed as

Adipose TissueBone and BonesRegenerationAnimalsCell-Free SystemHumansSkinangiogenesiscell-free fat extract (CEFFE)growth factorsreproductive healthtissue regenerationwound healing

Identifiers

PMID42543249
PMCPMC13429472

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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.