Control of Mesenchymal Cell Fate Via Application of FGF-8b in Vitro

Overview

Journal Stem Cell Res

Publisher Elsevier

Specialty Cell Biology

Date 2021 Jan 14

PMID 33445073

Citations 8

Authors

Takayoshi Otsuka

Paulos Y Mengsteab

Cato T Laurencin

Affiliations

Soon will be listed here.

Abstract

In order to develop strategies to regenerate complex tissues in mammals, understanding the role of signaling in regeneration competent species and mammalian development is of critical importance. Fibroblast growth factor 8 (FGF-8) signaling has an essential role in limb morphogenesis and blastema outgrowth. Therefore, we aimed to study the effect of FGF-8b on the proliferation and differentiation of mesenchymal stem cells (MSCs), which have tremendous potential for therapeutic use of cell-based therapy. Rat adipose derived stem cells (ADSCs) and muscle progenitor cells (MPCs) were isolated and cultured in growth medium and various types of differentiation medium (osteogenic, chondrogenic, adipogenic, tenogenic, and myogenic medium) with or without FGF-8b supplementation. We found that FGF-8b induced robust proliferation regardless of culture medium. Genes related to limb development were upregulated in ADSCs by FGF-8b supplementation. Moreover, FGF-8b enhanced chondrogenic differentiation and suppressed adipogenic and tenogenic differentiation in ADSCs. Osteogenic differentiation was not affected by FGF-8b supplementation. FGF-8b was found to enhance myofiber formation in rat MPCs. Overall, this study provides foundational knowledge on the effect of FGF-8b in the proliferation and fate determination of MSCs and provides insight in its potential efficacy for musculoskeletal therapies.

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References

Purushothaman S, Elewa A, Seifert A . Fgf-signaling is compartmentalized within the mesenchyme and controls proliferation during salamander limb development. Elife. 2019; 8. PMC: 6754229. DOI: 10.7554/eLife.48507. View

Groves J, Hammond C, Hughes S . Fgf8 drives myogenic progression of a novel lateral fast muscle fibre population in zebrafish. Development. 2005; 132(19):4211-22. DOI: 10.1242/dev.01958. View

Hutley L, Newell F, Kim Y, Luo X, Widberg C, Shurety W . A putative role for endogenous FGF-2 in FGF-1 mediated differentiation of human preadipocytes. Mol Cell Endocrinol. 2011; 339(1-2):165-71. DOI: 10.1016/j.mce.2011.04.012. View

Laurencin C, Khan Y . Regenerative engineering. Sci Transl Med. 2012; 4(160):160ed9. DOI: 10.1126/scitranslmed.3004467. View

Ogueri K, Jafari T, Escobar Ivirico J, Laurencin C . POLYMERIC BIOMATERIALS FOR SCAFFOLD-BASED BONE REGENERATIVE ENGINEERING. Regen Eng Transl Med. 2019; 5(2):128-154. PMC: 6697158. DOI: 10.1007/s40883-018-0072-0. View

Yun Y, Won J, Jeon E, Lee S, Kang W, Jo H . Fibroblast growth factors: biology, function, and application for tissue regeneration. J Tissue Eng. 2011; 2010:218142. PMC: 3042641. DOI: 10.4061/2010/218142. View

McCusker C, Bryant S, Gardiner D . The axolotl limb blastema: cellular and molecular mechanisms driving blastema formation and limb regeneration in tetrapods. Regeneration (Oxf). 2016; 2(2):54-71. PMC: 4895312. DOI: 10.1002/reg2.32. View

Xu X, Weinstein M, Li C, Naski M, Cohen R, Ornitz D . Fibroblast growth factor receptor 2 (FGFR2)-mediated reciprocal regulation loop between FGF8 and FGF10 is essential for limb induction. Development. 1998; 125(4):753-65. DOI: 10.1242/dev.125.4.753. View

Tang X, Saveh-Shemshaki N, Kan H, Khan Y, Laurencin C . Biomimetic electroconductive nanofibrous matrices for skeletal muscle regenerative engineering. Regen Eng Transl Med. 2021; 6(2):228-237. PMC: 7793553. DOI: 10.1007/s40883-019-00136-z. View

10.

Yablonka-Reuveni Z, Danoviz M, Phelps M, Stuelsatz P . Myogenic-specific ablation of Fgfr1 impairs FGF2-mediated proliferation of satellite cells at the myofiber niche but does not abolish the capacity for muscle regeneration. Front Aging Neurosci. 2015; 7:85. PMC: 4446549. DOI: 10.3389/fnagi.2015.00085. View

11.

Solchaga L, Penick K, Porter J, Goldberg V, Caplan A, Welter J . FGF-2 enhances the mitotic and chondrogenic potentials of human adult bone marrow-derived mesenchymal stem cells. J Cell Physiol. 2004; 203(2):398-409. DOI: 10.1002/jcp.20238. View

12.

Collins K, Lenz K, Pollitt E, Ferguson D, Hutson I, Springer L . Adipose tissue is a critical regulator of osteoarthritis. Proc Natl Acad Sci U S A. 2021; 118(1). PMC: 7817130. DOI: 10.1073/pnas.2021096118. View

13.

Westphal S, Gantert T, Kless C, Huttinger K, Klingenspor M, Fromme T . Fibroblast growth factor 8b induces uncoupling protein 1 expression in epididymal white preadipocytes. Sci Rep. 2019; 9(1):8470. PMC: 6560125. DOI: 10.1038/s41598-019-44878-w. View

14.

Satoh A, Makanae A, Nishimoto Y, Mitogawa K . FGF and BMP derived from dorsal root ganglia regulate blastema induction in limb regeneration in Ambystoma mexicanum. Dev Biol. 2016; 417(1):114-25. DOI: 10.1016/j.ydbio.2016.07.005. View

15.

McCusker C, Diaz-Castillo C, Sosnik J, Phan A, Gardiner D . Cartilage and bone cells do not participate in skeletal regeneration in Ambystoma mexicanum limbs. Dev Biol. 2016; 416(1):26-33. DOI: 10.1016/j.ydbio.2016.05.032. View

16.

Yu X, Mengsteab P, Narayanan G, Nair L, Laurencin C . Enhancing the Surface Properties of a Bioengineered Anterior Cruciate Ligament Matrix for Use with Point-of-Care Stem Cell Therapy. Engineering (Beijing). 2021; 7(2):153-161. PMC: 8205060. View

17.

Kragl M, Knapp D, Nacu E, Khattak S, Maden M, Epperlein H . Cells keep a memory of their tissue origin during axolotl limb regeneration. Nature. 2009; 460(7251):60-5. DOI: 10.1038/nature08152. View

18.

Christensen R, Weinstein M, Tassava R . Expression of fibroblast growth factors 4, 8, and 10 in limbs, flanks, and blastemas of Ambystoma. Dev Dyn. 2002; 223(2):193-203. DOI: 10.1002/dvdy.10049. View

19.

Abramoff B, Caldera F . Osteoarthritis: Pathology, Diagnosis, and Treatment Options. Med Clin North Am. 2020; 104(2):293-311. DOI: 10.1016/j.mcna.2019.10.007. View

20.

Wang R, Liu W, Du M, Yang C, Li X, Yang P . The differential effect of basic fibroblast growth factor and stromal cell‑derived factor‑1 pretreatment on bone morrow mesenchymal stem cells osteogenic differentiation potency. Mol Med Rep. 2018; 17(3):3715-3721. PMC: 5802181. DOI: 10.3892/mmr.2017.8316. View