Personalized Bone Organoid Using IPSC-derived Cells for Clinically Relevant Applications

Overview

Journal Res Sq

Date 2024 Dec 23

PMID 39711538

Authors

Qi Gao

Victoria Teissier

Wenjuan Zhu

Meagan J Makarcyzk

Issei Shinohara

Masatoshi Murayama

Yosuke Susuki

Simon Kwoon-Ho Chow

Bruce A Bunnell

Joy Wu

Hang Lin

Stuart B Goodman

Affiliations

Soon will be listed here.

Abstract

Patient-specific induced pluripotent stem cells (iPSCs)-based modeling potentially recapitulates the pathology and mechanisms more faithfully than cell line models and general animal models. Utilizing iPSC-derived cells for personalized bone formation research offers a powerful tool to better understand the role of individual differences in bone health and disease and provide more precise information for personalized bone regeneration therapies. Here we generated iPSC-derived mesenchymal progenitor cells (iMPCs), endothelial cells (iECs), and macrophages (iMØ), from different donors. Cellular markers, pluripotency properties, and immune regulatory properties were investigated. To replicate bone regeneration, we utilize different iPSC models and co-cultured three distinct cell types (iMPCs, iECs, and iMØ) in a 3D in vitro model derived from the same donor. Cells from different donors exhibited patient-specific characteristics and different regenerative capacities. Our study suggests that cells differentiated from iPSCs can be used to anticipate the effectiveness of cell-based therapies for personalized tissue regeneration.

References

Zhang Q, Chen B, Yan F, Guo J, Zhu X, Ma S . Interleukin-10 inhibits bone resorption: a potential therapeutic strategy in periodontitis and other bone loss diseases. Biomed Res Int. 2014; 2014:284836. PMC: 3947664. DOI: 10.1155/2014/284836. View

Sharma A, Sances S, Workman M, Svendsen C . Multi-lineage Human iPSC-Derived Platforms for Disease Modeling and Drug Discovery. Cell Stem Cell. 2020; 26(3):309-329. PMC: 7159985. DOI: 10.1016/j.stem.2020.02.011. View

Spiller K, Wrona E, Romero-Torres S, Pallotta I, Graney P, Witherel C . Differential gene expression in human, murine, and cell line-derived macrophages upon polarization. Exp Cell Res. 2015; 347(1):1-13. DOI: 10.1016/j.yexcr.2015.10.017. View

Cho K, Park M, Kim Y, Woo S, Ryu K . RNA sequencing reveals a transcriptomic portrait of human mesenchymal stem cells from bone marrow, adipose tissue, and palatine tonsils. Sci Rep. 2017; 7(1):17114. PMC: 5719355. DOI: 10.1038/s41598-017-16788-2. View

Mahon O, Browe D, Gonzalez-Fernandez T, Pitacco P, Whelan I, Von Euw S . Nano-particle mediated M2 macrophage polarization enhances bone formation and MSC osteogenesis in an IL-10 dependent manner. Biomaterials. 2020; 239:119833. DOI: 10.1016/j.biomaterials.2020.119833. View

Vinardell T, Sheehy E, Buckley C, Kelly D . A comparison of the functionality and in vivo phenotypic stability of cartilaginous tissues engineered from different stem cell sources. Tissue Eng Part A. 2012; 18(11-12):1161-70. PMC: 3360504. DOI: 10.1089/ten.TEA.2011.0544. View

Song Y, Lim J, Lim T, Im K, Kim N, Nam Y . Human mesenchymal stem cells derived from umbilical cord and bone marrow exert immunomodulatory effects in different mechanisms. World J Stem Cells. 2020; 12(9):1032-1049. PMC: 7524695. DOI: 10.4252/wjsc.v12.i9.1032. View

Yin J, Gong G, Sun C, Yin Z, Zhu C, Wang B . Angiopoietin 2 promotes angiogenesis in tissue-engineered bone and improves repair of bone defects by inducing autophagy. Biomed Pharmacother. 2018; 105:932-939. DOI: 10.1016/j.biopha.2018.06.078. View

Garelnabi M, Taylor-Smith L, Bielska E, Hall R, Stones D, May R . Quantifying donor-to-donor variation in macrophage responses to the human fungal pathogen Cryptococcus neoformans. PLoS One. 2018; 13(3):e0194615. PMC: 5875765. DOI: 10.1371/journal.pone.0194615. View

10.

Gordon S, Pluddemann A . Tissue macrophages: heterogeneity and functions. BMC Biol. 2017; 15(1):53. PMC: 5492929. DOI: 10.1186/s12915-017-0392-4. View

11.

Tsvetkova A, Vakhrushev I, Basok Y, Grigorev A, Kirsanova L, Lupatov A . Chondrogeneic Potential of MSC from Different Sources in Spheroid Culture. Bull Exp Biol Med. 2021; 170(4):528-536. DOI: 10.1007/s10517-021-05101-x. View

12.

Cao R, Eriksson A, Kubo H, Alitalo K, Cao Y, Thyberg J . Comparative evaluation of FGF-2-, VEGF-A-, and VEGF-C-induced angiogenesis, lymphangiogenesis, vascular fenestrations, and permeability. Circ Res. 2004; 94(5):664-70. DOI: 10.1161/01.RES.0000118600.91698.BB. View

13.

Satija R, Farrell J, Gennert D, Schier A, Regev A . Spatial reconstruction of single-cell gene expression data. Nat Biotechnol. 2015; 33(5):495-502. PMC: 4430369. DOI: 10.1038/nbt.3192. View

14.

Rhee H, Shaib A, Rehbach K, Lee C, Seif P, Thomas C . An Autaptic Culture System for Standardized Analyses of iPSC-Derived Human Neurons. Cell Rep. 2019; 27(7):2212-2228.e7. DOI: 10.1016/j.celrep.2019.04.059. View

15.

Hoffseth K, Busse E, Jaramillo J, Simkin J, Lacey M, Sammarco M . Age-Dependent Changes in Bone Architecture, Patterning, and Biomechanics During Skeletal Regeneration. Front Cell Dev Biol. 2021; 9:749055. PMC: 8548682. DOI: 10.3389/fcell.2021.749055. View

16.

Lin Z, Li Z, Li E, Li X, Del Duke C, Shen H . Osteochondral Tissue Chip Derived From iPSCs: Modeling OA Pathologies and Testing Drugs. Front Bioeng Biotechnol. 2020; 7:411. PMC: 6930794. DOI: 10.3389/fbioe.2019.00411. View

17.

Baghaei K, Hashemi S, Tokhanbigli S, Asadi Rad A, Assadzadeh-Aghdaei H, Sharifian A . Isolation, differentiation, and characterization of mesenchymal stem cells from human bone marrow. Gastroenterol Hepatol Bed Bench. 2017; 10(3):208-213. PMC: 5660271. View

18.

Koch S, Verhaegh F, Smink S, Mihaila S, Bouten C, Smits A . Donor Heterogeneity in the Human Macrophage Response to a Biomaterial Under Hyperglycemia . Tissue Eng Part C Methods. 2022; 28(8):440-456. DOI: 10.1089/ten.TEC.2022.0066. View

19.

Vogel D, Glim J, Stavenuiter A, Breur M, Heijnen P, Amor S . Human macrophage polarization in vitro: maturation and activation methods compared. Immunobiology. 2014; 219(9):695-703. DOI: 10.1016/j.imbio.2014.05.002. View

20.

Olmsted-Davis E, Mejia J, Salisbury E, Gugala Z, Davis A . A Population of M2 Macrophages Associated With Bone Formation. Front Immunol. 2021; 12:686769. PMC: 8547272. DOI: 10.3389/fimmu.2021.686769. View