Cited by 12Tissue Engineering and Regenerative Medicine3D Printing in Biomedical ResearchBone Tissue Engineering Materials

Decellularized Splenic Matrix as a Scaffold for Spleen Bioengineering

Open access
Zanardo, Tadeu Ériton Caliman, Amorim, Fernanda Gobbi, Taufner, Gabriel Henrique, Pereira, Rayssa Helena Arruda, Baiense, Ian Manhoni, Destefani, Afrânio Côgo, Iwai, Leo Kei, Maranhão, Raul Cavalcante +1 more·2020·Frontiers in Bioengineering and Biotechnology

Abstract

The spleen is considered a non-essential organ. However, its importance is increasingly clear, given the serious disorders caused by its absence or dysfunction, e.g., greater susceptibility to infections, thromboembolism and cancer. Surgical techniques to preserve the spleen and maintain splenic function have become increasingly common. However, the morbidity and mortality associated with its absence and dysfunction are still high. We used the decellularization technique to obtain a viable splenic scaffold for recellularization in vitro and propose the idea of bioengineered spleen transplantation to the host. We observed the maintenance of important structural components such as white pulp, marginal zone and red pulp, in addition to the network of vascular ducts. The decellularized scaffold presents minimal residual DNA and SDS, which are essential to prevent immunogenic responses and transplantation failure. Also, the main components of the splenic matrix were preserved after decellularization, with retention of approximately 72% in the matrisomal protein content. The scaffold we developed was partially recellularized with stromal cells from the spleen of neonatal rats, demonstrating adhesion, proliferation and viability of cells. Therefore, the splenic scaffold is very promising for use in studies on spleen reconstruction and transplantation, with the aim of complete recovery of splenic function.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.3389/fbioe.2020.573461

Cites

2 of 2 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Splenic dECM scaffolds have shown promising results for bioengineering the liver and pancreas.

    “In one successful example, splenic dECM scaffolds have shown promising results for bioengineering the liver and pancreas. However, further studies should be done on this idea before translation into the clinic [230, 231].”

    From Immunogenicity of decellularized extracellular matrix scaffolds: a bottleneck in tissue engineering and regenerative medicine (2023) · cites this paper as [231]

    The Discussion (page unavailable) says that other studies used decellularized splenic matrix as a scaffold to restore liver and pancreas function. It does not report those studies’ results or establish that they succeeded, so the claim of promising results goes beyond what this paper says. (LLM, conf=0.83)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 47

  1. Aamodt J. M. Grainger D. W. (2016). Extracellular matrix-based biomaterial scaffolds and the host response. Biomaterials 86 68– 82. 10.1016/j.biomaterials.2016.02.003 26890039 PMC4785021 · DOI · Paper page
  2. Barallobre-Barreiro J. Baig F. Fava M. Yin X. Mayr M. (2017). Glycoproteomics of the extracellular matrix: a method for intact glycopeptide analysis using mass spectrometry. J. Vis. Exp. 2017: 55674. PMC5565024 28518125
  3. Bronte V. Pittet M. J. (2013). The spleen in local and systemic regulation of immunity. Immunity 39 806– 818. 10.1016/j.immuni.2013.10.010 24238338 PMC3912742 · DOI
  4. Bruford M. W. Hanotte O. Brookfield J. F. Y. Burke T. (1992). “ Multi and single locus DNA fingerprinting,” in Molecular Analysis of Populations: A Practical Approach, ed. Hoelzel A. R. (Oxford: IRL Press), 225– 269.
  5. Chan J. F.-W. Zhang A. J. Yuan S. Poon V. K. Chan C. C. Lee A. C. (2020). Simulation of the clinical and pathological manifestations of Coronavirus Disease 2019 (COVID-19) in golden Syrian hamster model: implications for disease pathogenesis and transmissibility. Clin. Infect. Dis. Online ahead of print PMC7184405 32215622
  6. Connell N. T. Brunner A. M. Kerr C. A. Schiffman F. J. (2011). Splenosis and sepsis: the born-again spleen provides poor protection. Virulence. 2 4– 11. 10.4161/viru.2.1.14611 21224728 · DOI
  7. Crapo P. M. Gilbert T. W. Badylak S. F. (2011). An overview of tissue and whole organ decellularization processes. Biomaterials 32 3233– 3243. 10.1016/j.biomaterials.2011.01.057 21296410 PMC3084613 · DOI · Paper page
  8. Di Sabatino A. Carsetti R. Corazza G. R. (2011). Post-splenectomy and hyposplenic states. Lancet 378 86– 97. 10.1016/s0140-6736(10)61493-6 21474172 · DOI
  9. Gao R. Wu W. Xiang J. Lv Y. Zheng X. Chen Q. (2015). Hepatocyte culture in autologous decellularized spleen matrix. Organogenesis 11 16– 29. 10.1080/15476278.2015.1011908 25664568 PMC4594376 · DOI
  10. Garreta E. Oria R. Tarantino C. Pla-Roca M. Prado P. Fernández-Avilés F. (2017). Tissue engineering by decellularization and 3D bioprinting. Mater. Today 20 166– 178. 10.1016/j.mattod.2016.12.005 · DOI
  11. Gilpin A. Yang Y. (2017). Decellularization strategies for regenerative medicine: from processing techniques to applications. Biomed. Res. Int. 2017: 9831534. PMC5429943 28540307
  12. Guan W. Ni Z. Hu Y. Liang W. Ou C. He J. (2020). Clinical characteristics of coronavirus disease 2019 in China. N. Engl. J. Med. 382 1708– 1720. 32109013 PMC7092819
  13. Heath D. E. (2019). A review of decellularized extracellular matrix biomaterials for regenerative engineering applications. Regen. Eng. Transl. Med. 5 155– 166. 10.1007/s40883-018-0080-0 PMC11978403 40201194 · DOI
  14. Hillebrandt K. H. Everwien H. Haep N. Keshi E. Pratschke J. Sauer I. M. (2019). Strategies based on organ decellularization and recellularization. Transpl. Int. 32 571– 585. 31099920
  15. Hussey G. S. Dziki J. L. Badylak S. F. (2018). Extracellular matrix-based materials for regenerative medicine. Nat. Rev. Mater. 3 159– 173. 10.1038/s41578-018-0023-x · DOI · Paper page
  16. Karlsson M. Björnsson S. (2001). “ Quantitation of proteoglycans in biological fluids using alcian blue,” in Proteoglycan Protocols. Methods in Molecular BiologyTM, Vol. 171, ed. Iozzo R. V. (Humana Press: New Jersey). 10.1385/1-59259-209-0:159 11450226 · DOI
  17. Krasny L. Paul A. Wai P. Howard B. A. Natrajan R. C. Huang P. H. (2016). Comparative proteomic assessment of matrisome enrichment methodologies. Biochem. J. 473 3979– 3995. 10.1042/bcj20160686 27589945 PMC5095915 · DOI
  18. Kristinsson S. Y. Gridley G. Hoover R. N. Check D. Landgren O. (2014). Long-term risks after splenectomy among 8,149 cancer-free American veterans: a cohort study with up to 27 years follow-up. Haematologica 99 392– 398. 10.3324/haematol.2013.092460 24056815 PMC3912973 · DOI
  19. Kyaw M. H. Holmes E. M. Toolis F. Wayne B. Chalmers J. Jones I. G. (2006). Evaluation of severe infection and survival after splenectomy. Am. J. Med. 119: 276.e1– e7. 16490477
  20. Li Q. Uygun B. E. Geerts S. Ozer S. Scalf M. Gilpin S. E. (2016). Proteomic analysis of naturally-sourced biological scaffolds. Biomaterials 75 37– 46. 10.1016/j.biomaterials.2015.10.011 26476196 PMC4644483 · DOI
  21. Liu P. Tian B. Yang L. Zheng X. Zhang X. Li J. (2019). Hemocompatibility improvement of decellularized spleen matrix for constructing transplantable bioartificial liver. Biomed. Mater. 14: 025003. 10.1088/1748-605x/aaf375 30523825 · DOI
  22. Lokmic Z. Lämmermann T. Sixt M. Cardell S. Hallmann R. Sorokin L. (2008). The extracellular matrix of the spleen as a potential organizer of immune cell compartments. Semin. Immunol. 20 4– 13. 10.1016/j.smim.2007.12.009 18243017 · DOI
  23. Mao A. S. Mooney D. J. (2015). Regenerative medicine: current therapies and future directions. Proc. Natl. Acad. Sci. U.S.A. 112 14452– 14459. 26598661 PMC4664309
  24. Mellemkjaer L. Olsen J. H. Linet M. S. Gridley G. McLaughlin J. K. (1995). Cancer risk after splenectomy. Ugeskr. Laeger 157 5097– 5100. 7502377
  25. Miranda-Nieves D. Chaikof E. L. (2017). Collagen and elastin biomaterials for the fabrication of engineered living tissues. ACS Biomater. Sci. Eng. 3 694– 711. 10.1021/acsbiomaterials.6b00250 33440491 · DOI
  26. Nakayama K. H. Batchelder C. A. Lee C. I. Tarantal A. F. (2010). Decellularized rhesus monkey kidney as a three-dimensional scaffold for renal tissue engineering. Tissue Eng. Part A 16 2207– 2216. 10.1089/ten.tea.2009.0602 20156112 PMC2947947 · DOI
  27. Nara S. Chameettachal S. Midha S. Murab S. Ghosh S. (2016). Preservation of biomacromolecular composition and ultrastructure of a decellularized cornea using a perfusion bioreactor. RSC Adv. 6 2225– 2240. 10.1039/c5ra20745b · DOI · Paper page
  28. Nguyen D. T. O’Hara M. Graneli C. Hicks R. Miliotis T. Nyström A. (2018). Humanizing miniature hearts through 4-flow cannulation perfusion decellularization and recellularization. Sci. Rep. 8: 7458. PMC5945628 29748585
  29. Ott H. C. Matthiesen T. S. Goh S.-K. Black L. D. Kren S. M. Netoff T. I. (2008). Perfusion-decellularized matrix: using nature’s platform to engineer a bioartificial heart. Nat. Med. 14 213– 221. 10.1038/nm1684 18193059 · DOI · Paper page
  30. Perea-Gil I. Gálvez-Montón C. Prat-Vidal C. Jorba I. Segú-Vergés C. Roura S. (2018). Head-to-head comparison of two engineered cardiac grafts for myocardial repair: from scaffold characterization to pre-clinical testing. Sci. Rep. 8: 6708. PMC5928167 29712965
  31. Robertson M. J. Soibam B. O’Leary J. G. Sampaio L. C. Taylor D. A. (2018). Recellularization of rat liver: an in vitro model for assessing human drug metabolism and liver biology. PLoS One 13: e0191892. 10.1371/journal.pone.0191892 29377912 PMC5788381 · DOI
  32. Sackett S. D. Tremmel D. M. Ma F. Feeney A. K. Maguire R. M. Brown M. E. (2018). Extracellular matrix scaffold and hydrogel derived from decellularized and delipidized human pancreas. Sci. Rep. 8: 10452. PMC6041318 29993013
  33. Samuel C. S. (2009). Determination of collagen content, concentration, and sub-types in kidney tissue. Methods Mol. Biol. 466 223– 235. 10.1007/978-1-59745-352-3_16 19148607 · DOI
  34. Song J. Lokmic Z. Lämmermann T. Rolf J. Wu C. Zhang X. (2013). Extracellular matrix of secondary lymphoid organs impacts on B-cell fate and survival. Proc. Natl. Acad. Sci. U.S.A. 110 E2915– E2924. 23847204 PMC3732919
  35. Sun L.-M. Chen H.-J. Jeng L.-B. Li T.-C. Wu S.-C. Kao C.-H. (2015). Splenectomy and increased subsequent cancer risk: a nationwide population-based cohort study. Am. J. Surg. 210 243– 251. 10.1016/j.amjsurg.2015.01.017 25986002 · DOI
  36. Tan J. K. H. Watanabe T. (2014). Murine spleen tissue regeneration from neonatal spleen capsule requires lymphotoxin priming of stromal cells. J. Immunol. 193 1194– 1203. 10.4049/jimmunol.1302115 24951816 PMC4105237 · DOI
  37. Tan J. K. H. Watanabe T. (2017). Stromal cell subsets directing neonatal spleen regeneration. Sci. Rep. 7: 40401. PMC5220291 28067323
  38. Taniguchi L. U. Correia M. D. T. Zampieri F. G. (2014). Overwhelming post-splenectomy infection: narrative review of the literature. Surg. Infect. 15 686– 693. 10.1089/sur.2013.051 25318011 · DOI
  39. Thomsen R. W. (2009). Risk for hospital contact with infection in patients with splenectomy. Ann. Intern. Med. 151: 546. 10.7326/0003-4819-151-8-200910200-00008 19841456 · DOI
  40. Vishwakarma S. K. Lakkireddy C. Bardia A. Basha Paspala S. A. Tripura C. Habeeb M. A. (2019). Biofabricated humanized insulin producing neo-organs generates secondary neo-organoids through ectopic transplantation. Cell Mol. Bioeng. 12 569– 582. 10.1007/s12195-019-00586-z · DOI
  41. Walker C. Mojares E. Del Río Hernández A. (2018). Role of extracellular matrix in development and cancer progression. Int. J. Mol. Sci. 19: 3028. 10.3390/ijms19103028 30287763 PMC6213383 · DOI
  42. Xiang J. Zheng X. Gao R. Wu W. Q. Zhu X. L. Li J. H. (2015). Liver regeneration using decellularized splenic scaffold: a novel approach in tissue engineering. Hepatobiliary Pancreat Dis. Int. 14 502– 508. 10.1016/s1499-3872(15)60423-4 26459726 · DOI
  43. Xiang J. Zheng X. Liu P. Yang L. Dong D. Wu W. (2016). Decellularized spleen matrix for reengineering functional hepatic-like tissue based on bone marrow mesenchymal stem cells. Organogenesis 12 128– 142. 10.1080/15476278.2016.1185584 27158925 PMC4993304 · DOI
  44. Xu X. Chang X. N. Pan H. X. Su H. Huang B. Yang M. (2020). Pathological changes of the spleen in ten patients with new coronavirus infection by minimally invasive autopsies. Chinese J. Pathol. 49 576– 582. 32340089
  45. Yang H. Yang S. Kong J. Dong A. Yu S. (2015). Obtaining information about protein secondary structures in aqueous solution using Fourier transform IR spectroscopy. Nat. Protoc. 10 382– 396. 10.1038/nprot.2015.024 25654756 · DOI
  46. Zheng X.-L. Xiang J.-X. Wu W.-Q. Wang B. Liu W. Y. Gao R. (2015). Using a decellularized splenic matrix as a 3D scaffold for hepatocyte cultivation in vitro: a preliminary trial. Biomed. Mater. 10: 045023 10.1088/1748-6041/10/4/045023 26290516 · DOI
  47. Zvarova B. Uhl F. E. Uriarte J. J. Borg Z. D. Coffey A. L. Bonenfant N. R. (2016). Residual detergent detection method for nondestructive cytocompatibility evaluation of decellularized whole lung scaffolds. Tissue Eng. Part. C Methods 22 418– 428. 10.1089/ten.tec.2015.0439 26905643 PMC4870652 · DOI

Cited by

Sorted by citations

Authors
Zanardo, T. É. C., Amorim, F. G., Taufner, G. H., Pereira, R. H. A., Baiense, I. M., Destefani, A. C., Iwai, L. K., Maranhão, R. C., & Nogueira, B. V.
Affiliations
  • Universidade Federal do Espírito Santo (BR)
  • Universidade Vila Velha (BR)
  • Instituto Butantan (BR)
  • Universidade de São Paulo (BR)
Corresponding author
Nogueira, Breno Valentim
Venue
Frontiers in Bioengineering and Biotechnology
Published
2020-10-02
Volume
8
Pages
573461-573461
ISSN
2296-4185 (ISSN-L)
OpenAlex
W3091183117
Cited by
12
References
2
Citations by year
2026: 2 · 2025: 1 · 2024: 3 · 2023: 4 · 2022: 2
FWCI
1.37
Type
journal article
Language
en
Open access
Locations
  • Frontiers in Bioengineering and Biotechnology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Fundação de Amparo à Pesquisa do Estado de São Paulo (13/07467-1, 17/17943-6, 16/04000-3, 2013/07467, 2013/074671)
  • Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (2013/07467-1, (Code 001), 001), and)
  • Conselho Nacional de Desenvolvimento Científico e Tecnológico (/2019-0, 2018‐3, 2013/07467‐1)
  • Fundação de Amparo à Pesquisa e Inovação do Espírito Santo (2013/07467-1, Code 001)
Topics
  • Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
  • Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
  • Physical Sciences › Engineering › Biomedical Engineering › Bone Tissue Engineering Materials
Keywords
decellularization, spleen transplantation, recellularization, splenic stromal cells, splenic white pulp, splenic red pulp, marginal zone, immunogenicity

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review