Definition and research guide
This page combines a MeSH definition, publication statistics and selected research abstracts. It is a starting point for reading the literature, not a medical textbook or a systematic evidence review.
Content available: 3 complete abstracts (531 words), 9 references. Full article text is not stored or reproduced here; follow the PMID, DOI or PMC links to read the original sources and their access terms.
Definition
Interstitial space between cells, occupied by interstitial fluid as well as amorphous and fibrous substances. For organisms with a cell wall, the extracellular space includes everything outside of the cell membrane including the periplasm and the cell wall.
Definition: NLM Medical Subject Headings (MeSH) scope note (Public domain (U.S. National Library of Medicine); attribution requested). View the MeSH record.
Also known as: Extracellular Spaces; Space, Extracellular; Spaces, Extracellular; Intercellular Space; Intercellular Spaces; Space, Intercellular; Spaces, Intercellular.
Where it fits in the MeSH classification
- Broader topics
- Body Fluid Compartments; Cellular Structures
- Narrower topics
- Extracellular Fluid; Extracellular Matrix; Extracellular Traps; Extracellular Vesicles; Periplasm
Related concepts
- Extracellular Fluid
- Cell Wall
- Cell Membrane
- Periplasm
Research landscape
PubMed indexes 158,957 records tagged with the MeSH heading “Extracellular Space” (counts retrieved 2026-10-31). 52,599 of them (33.1%) were published from 2020 onward, and the busiest period so far is 2020 onward with 52,599 records.
Reviews account for 27,732 records (17.4%) and meta-analyses for 256. Randomized controlled trials number 619 (0.4%) as a share of all records on the topic. Randomized trials make up only a small share of this literature, so much of what is known comes from laboratory, observational or descriptive work.
Show the data
| Period | Records |
|---|---|
| through 1999 | 40,590 |
| 2000-2009 | 24,350 |
| 2010-2019 | 41,418 |
| 2020 onward | 52,599 |
Publication-type chart data
| Type | Records | Share |
|---|---|---|
| Reviews | 27,732 | 17.4% |
| Meta-analyses | 256 | 0.2% |
| Randomized controlled trials | 619 | 0.4% |
Method: PubMed query "Extracellular Space"[MeSH Terms] with publication-type and date filters, retrieved 2026-10-31.
Reading the evidence in anatomy and physiology
Anatomy describes how body structures are built and physiology describes how they normally work, so most findings here are descriptive or mechanistic rather than evidence about treatment. Much of what is known comes from dissection, imaging, tissue studies and experiments in animals, and measurements in healthy volunteers can differ from those in people with disease or at different ages. Normal ranges vary between individuals and populations. Check whether a result was measured in people or in another species, the age and health of the participants, and the method used.
Evidence from open-access studies
These open-access studies come from PubMed’s best-match results for this heading (papers whose main topic it is), ranked here by citation count, with one recent addition. Each abstract is reproduced in full under its recorded open licence so that you can read the authors’ own words. They illustrate the literature; they are not a systematic summary of it. Citation counts measure attention, not reliability or clinical benefit.
| Study / authors | Year | Source label / design | Europe PMC citations | Licence / source |
|---|---|---|---|---|
| Developmental Scarcity Induces Sex Differences in Social Recognition and CA2 Perineuronal Nets | 2026 | Research article Design not recorded in structured metadata | 2 | cc by PMID 42692858 · DOI · PMC13592735 |
| Ovarian Extracellular Matrix Mechanics Regulate Oocyte-Follicle Interactions During Female Reproductive Aging | 2026 | Research article Design not recorded in structured metadata | 2 | cc by PMID 42593156 · DOI · PMC13471645 |
| Ovarian hormone loss modifies the nucleic acid cargo of circulating extracellular vesicles and skeletal muscle metabolism after acute exercise in rats | 2026 | Research article Design not recorded in structured metadata | 1 | cc by PMID 42574568 · DOI · PMC13456521 |
Developmental Scarcity Induces Sex Differences in Social Recognition and CA2 Perineuronal Nets [1]
Abstract reading summary — source excerpts
- Opening excerpt
- Early-life adversity (ELA) has a lasting negative impact on social behavior in both humans and rodents.
- Closing excerpt
- Focal degradation of the extracellular matrix in the CA2 region restored social recognition function in adult males previously subjected to early stress, suggesting that the effects of developmental adversity may be improved by targeted intervention in adulthood.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (148 words)
Early-life adversity (ELA) has a lasting negative impact on social behavior in both humans and rodents. Sex differences exist in functional outcomes of postnatal stress, but underlying mechanisms remain incompletely explored. Using the limited bedding and nesting paradigm, a mouse model of developmental scarcity, we found sex differences in social behavior with adult males showing impaired social recognition and adult females showing intact social recognition with enhanced social novelty preference. Perineuronal nets (PNNs), specialized extracellular matrix structures, are known to inhibit developmental plasticity and are concentrated in the CA2 region of the hippocampus in adulthood. We found higher intensity of CA2 PNNs in adult males, but not adult females, after ELA. Focal degradation of the extracellular matrix in the CA2 region restored social recognition function in adult males previously subjected to early stress, suggesting that the effects of developmental adversity may be improved by targeted intervention in adulthood.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 42692858 · DOI · PMC13592735
Ovarian Extracellular Matrix Mechanics Regulate Oocyte-Follicle Interactions During Female Reproductive Aging [2]
Abstract reading summary — source excerpts
- Opening excerpt
- Female reproductive aging is associated with ovarian functional decline, leading to infertility.
- Closing excerpt
- These findings provide mechanistic insight into how changes in ECM mechanics contribute to ovarian aging functional decline and reveal potential therapeutic targets to counter fertility loss associated with tissue aging and fibrosis.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (182 words)
Female reproductive aging is associated with ovarian functional decline, leading to infertility. During aging, biochemical and biophysical changes in the ovarian extracellular matrix (ECM) occur, yet how these properties affect follicle growth and oocyte quality remains poorly understood. Here we describe spatiotemporal changes in the ovarian ECM with age using mass spectrometry, immunohistochemistry, and nanoindentation. While follicle stiffness remains unchanged, stromal matrix remodeling is associated with a ~2.5-fold increase in stiffness. To understand how this increase in stromal stiffness affects age-related follicular dysfunction, isolated young follicles were cultured in soft and stiff hydrogels mimicking young and aged ovarian stromal stiffness, respectively. Higher stiffness lead to a decrease in granulosa cell (GC) proliferation, oocyte quality, and GC-oocyte interactions mediated via transzonal projections (TZPs). RNA-seq revealed TGF-β signaling as a major pathway affected by stiffness, and activation of TGF-β signaling through Smad7 silencing rescued TZP formation and oocyte quality in stiff matrix. These findings provide mechanistic insight into how changes in ECM mechanics contribute to ovarian aging functional decline and reveal potential therapeutic targets to counter fertility loss associated with tissue aging and fibrosis.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 42593156 · DOI · PMC13471645
Ovarian hormone loss modifies the nucleic acid cargo of circulating extracellular vesicles and skeletal muscle metabolism after acute exercise in rats [3]
Abstract reading summary — source excerpts
- Opening excerpt
- Loss of ovarian hormones (i.
- Closing excerpt
- Finally, we demonstrate that the loss of ovarian hormones leads to higher anaerobic energy production during an acute bout of exercise, implicating an inferior ability to sustain aerobic energy production during exercise.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (201 words)
Loss of ovarian hormones (i.e., menopause) leads to negative effects on metabolic health. While exercise offers significant benefits, it seems to be insufficient to completely reverse these changes. The mechanisms by which exercise conveys the effects throughout the body are still poorly understood. Extracellular vesicles (EVs) are released into circulation during exercise. EVs carry small non-coding RNAs (sRNAs), such as microRNAs (miRs), which are proposed as mediators of the effects of exercise. We have previously shown that the miR response to acute exercise of EVs and high-density lipoprotein (HDL) is diminished in postmenopausal women with low oestrogen levels, which we were able to replicate here also in a rat model. In this study, we examined the effect of loss of ovarian hormones and acute exercise in the sRNA cargo of EV and HDL particles in female rats. We show for the first time that loss of ovarian hormones affects specifically the nucleic acid cargo of circulating EVs. We further show that the oestrogen responsive miRs regulate anaerobic glycolytic pathway. Finally, we demonstrate that the loss of ovarian hormones leads to higher anaerobic energy production during an acute bout of exercise, implicating an inferior ability to sustain aerobic energy production during exercise.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 42574568 · DOI · PMC13456521
Key reviews and meta-analyses
The most cited review-type papers among PubMed’s best-match results for this heading, listed with bibliographic details only. Follow the links for the full text and access terms.
- Research article MIBlood-EV: Minimal information to enhance the quality and reproducibility of blood extracellular vesicle research [4]
- Research article A systematic review and meta-analysis of clinical trials assessing safety and efficacy of human extracellular vesicle-based therapy [5]
- Research article Cell-Derived Microparticles in Patients with Type 2 Diabetes Mellitus: a Systematic Review and Meta-Analysis [6]
- Research article Role of Exosomes in Dermal Wound Healing: A Systematic Review [7]
- Research article Efficacy and safety of small extracellular vesicle interventions in wound healing and skin regeneration: A systematic review and meta-analysis of animal studies [8]
- Research article Assisted hatching of human embryos: a systematic review and meta-analysis of randomized controlled trials [9]
References
- Waters RC, Gore IR, Brown CJ, Skweres-Gilmartin AL, Rathaur AB, Gould E. Developmental Scarcity Induces Sex Differences in Social Recognition and CA2 Perineuronal Nets. . 2026. PMID 42692858 · DOI · PMC13592735
- Shen X, Wang H, Cao G, Lee Y, Zhu J, Wang LC, et al.. Ovarian Extracellular Matrix Mechanics Regulate Oocyte-Follicle Interactions During Female Reproductive Aging. . 2026. PMID 42593156 · DOI · PMC13471645
- Puumalainen V, Maja A, Korhonen TM, Nissinen TA, Hulkko E, Ihalainen JA, et al.. Ovarian hormone loss modifies the nucleic acid cargo of circulating extracellular vesicles and skeletal muscle metabolism after acute exercise in rats. . 2026. PMID 42574568 · DOI · PMC13456521
- Lucien F, Gustafson D, Lenassi M, Li B, Teske JJ, Boilard E, et al.. MIBlood-EV: Minimal information to enhance the quality and reproducibility of blood extracellular vesicle research. J Extracell Vesicles. 2023. PMID 38063210 · DOI · PMC10704543
- Van Delen M, Derdelinckx J, Wouters K, Nelissen I, Cools N. A systematic review and meta-analysis of clinical trials assessing safety and efficacy of human extracellular vesicle-based therapy. J Extracell Vesicles. 2024. PMID 38958077 · DOI · PMC11220457
- Li S, Wei J, Zhang C, Li X, Meng W, Mo X, et al.. Cell-Derived Microparticles in Patients with Type 2 Diabetes Mellitus: a Systematic Review and Meta-Analysis. Cell Physiol Biochem. 2016. PMID 27832642 · DOI
- Prasai A, Jay JW, Jupiter D, Wolf SE, El Ayadi A. Role of Exosomes in Dermal Wound Healing: A Systematic Review. J Invest Dermatol. 2022. PMID 34461128 · DOI · PMC9400548
- Al-Masawa ME, Alshawsh MA, Ng CY, Ng AMH, Foo JB, Vijakumaran U, et al.. Efficacy and safety of small extracellular vesicle interventions in wound healing and skin regeneration: A systematic review and meta-analysis of animal studies. Theranostics. 2022. PMID 36185607 · DOI · PMC9516230
- Martins WP, Rocha IA, Ferriani RA, Nastri CO. Assisted hatching of human embryos: a systematic review and meta-analysis of randomized controlled trials. Hum Reprod Update. 2011. PMID 21474527 · DOI
About this article
- Sources
- NLM Medical Subject Headings (definition, synonyms); NCBI PubMed (counts, identifiers); Europe PMC (open-access abstracts and citation counts).
- Verification
- Every reference was resolved against PubMed on 2026-10-31; title, year and DOI matched.
- Review state
- automated source verified; no human expert review has been recorded yet.
- Version
- 1, last updated 2026-10-31.
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Evidence strength
EvidenceHelix's computed view of the study designs behind this topic: how common meta-analyses, randomized trials and reviews are, how recent the literature is, and a plain-language reading. It describes the design mix of the literature. It is not a quality appraisal of any study, and it is not medical advice.