The Impact of Cellular Microenvironments and Biomaterials on Induced Pluripotent Stem Cell Generation


Journal of Smart and Sustainable Farming

Received On : 12 April 2025

Revised On : 02 June 2025

Accepted On : 30 June 2025

Published On : 30 July 2025

Volume 01, 2025

Pages : 119-130


PDF
Download

DOI
https://doi.org/10.64026/JSSF/2025012
Article Views
Abstract

The implications of the microenvironment in reprogramming and cellular differentiation are very important and should not be overlooked. All components from the extracellular matrix (ECM) to physical properties of biomaterials play a significant role. Mechanotransduction, which happens through integrins and adapter proteins refers to cells’ ability to sense mechanical stimuli. Studies have demonstrated that ECM stiffness affects fate and specification of cells. Similarly, composition of biomaterials such as toughness, diameter of fibers, and substrate topography may influence reprogramming process and cell growth. Therefore, when signaling molecules like growth factors are introduced, ECM composition may be critical in determining cell fate. Matrigels made from fibrous protein called fibrinogen or collagen display an apt medium for growth and differentiation during stem cell research over time. The paper discusses how microenvironmental factors control motility and cellular determination in detail. The article explores the distinct impacts of mechanical stimulation and nanotopography on the regulation of stem cells inside the extracellular matrix. Finally, it highlights that altering biomaterials may predestine the cell fate after they have been reprogrammed into a pluripotent state, since they induce pluripotency inside embryonic bodies. This comprehensive article provides information on the principles that impact regenerative medicine concerns, specifically in terms of stem cell biology.

Keywords

Induced Pluripotent Stem Cells, Embryonic Stem Cells, Extracellular Matrix, Endothelial Progenitor Cells, Mesenchymal Stem Cells.

  1. R. Ramprasad, B. Chaudhary, and R. Bandopadhyay, “Induced Pluripotent Stem Cells—A milestone in Regenerative Medicine: 2012 Nobel Prize for Physiology or Medicine,” National Academy Science Letters, vol. 37, no. 2, pp. 203–206, Mar. 2014, doi: 10.1007/s40009-013-0214-3.
  2. J. Lewandowski and M. Kurpisz, “Techniques of human embryonic stem cell and induced pluripotent stem cell derivation,” Archivum Immunologiae Et Therapiae Experimentalis, vol. 64, no. 5, pp. 349–370, Mar. 2016, doi: 10.1007/s00005-016-0385-y.
  3. C. V. Echegaray and A. Guberman, “Nanog in iPS cells and during reprogramming,” in Elsevier eBooks, 2022, pp. 319–348. doi: 10.1016/b978-0-323-90059-1.00006-3.
  4. S. W. Plouffe et al., “The Hippo pathway effector proteins YAP and TAZ have both distinct and overlapping functions in the cell,” Journal of Biological Chemistry, vol. 293, no. 28, pp. 11230–11240, Jul. 2018, doi: 10.1074/jbc.ra118.002715.
  5. J. Keung, P. Asuri, S. Kumar, and D. V. Schaffer, “Soft microenvironments promote the early neurogenic differentiation but not self-renewal of human pluripotent stem cells,” Integrative Biology, vol. 4, no. 9, pp. 1049–1058, Aug. 2012, doi: 10.1039/c2ib20083j.
  6. H. J. Kong and D. J. Mooney, “Microenvironmental regulation of biomacromolecular therapies,” Nature Reviews Drug Discovery, vol. 6, no. 6, pp. 455–463, Jun. 2007, doi: 10.1038/nrd2309.
  7. G. Liu, B. T. David, M. Trawczynski, and R. G. Fessler, “Advances in Pluripotent stem cells: history, mechanisms, technologies, and applications,” Stem Cell Reviews and Reports, vol. 16, no. 1, pp. 3–32, Nov. 2019, doi: 10.1007/s12015-019-09935-x.
  8. L. Galarza, T. E. Arshaghi, A. O’Brien, A. Ivanovska, and F. Barry, “Induced pluripotent stem cells in companion animals: how can we move the field forward?,” Frontiers in Veterinary Science, vol. 10, Apr. 2023, doi: 10.3389/fvets.2023.1176772.
  9. Z. Jiang, H. Yun, and X. Cao, “Induced pluripotent stem cell (iPSCs) and their application in immunotherapy,” Cellular & Molecular Immunology, vol. 11, no. 1, pp. 17–24, Dec. 2013, doi: 10.1038/cmi.2013.62.
  10. M. Yamoah, P. N. Thai, and X.-D. Zhang, “Transgene delivery to human induced pluripotent stem cells using nanoparticles,” Pharmaceuticals, vol. 14, no. 4, p. 334, Apr. 2021, doi: 10.3390/ph14040334.
  11. J. Mao et al., “Reprogramming stem cells in regenerative medicine,” Smart Medicine, vol. 1, no. 1, Dec. 2022, doi: 10.1002/smmd.20220005.
  12. Zhang et al., “Zero-dimensional, one-dimensional, two-dimensional and three-dimensional biomaterials for cell fate regulation,” Advanced Drug Delivery Reviews, vol. 132, pp. 33–56, Jul. 2018, doi: 10.1016/j.addr.2018.06.020.
  13. Barui, F. Chowdhury, A. Pandit, and P. Datta, “Rerouting mesenchymal stem cell trajectory towards epithelial lineage by engineering cellular niche,” Biomaterials, vol. 156, pp. 28–44, Feb. 2018, doi: 10.1016/j.biomaterials.2017.11.036.
  14. H. S. Gerardo et al., “Soft culture substrates favor stem-like cellular phenotype and facilitate reprogramming of human mesenchymal stem/stromal cells (hMSCs) through mechanotransduction,” Scientific Reports, vol. 9, no. 1, Jun. 2019, doi: 10.1038/s41598-019-45352-3.
  15. M. Caiazzo, Y. Okawa, A. Ranga, A. Piersigilli, Y. Tabata, and M. P. Lütolf, “Defined three-dimensional microenvironments boost induction of pluripotency,” Nature Materials, vol. 15, no. 3, pp. 344–352, Jan. 2016, doi: 10.1038/nmat4536.
  16. S. Romanazzo, L. Kang, P. Srivastava, and K. A. Kilian, “Targeting cell plasticity for regeneration: From in vitro to in vivo reprogramming,” Advanced Drug Delivery Reviews, vol. 161–162, pp. 124–144, Jan. 2020, doi: 10.1016/j.addr.2020.08.007.
  17. K. Shukla, G. Gao, and B. S. Kim, “Applications of 3D bioprinting technology in induced Pluripotent Stem Cells-Based tissue engineering,” Micromachines, vol. 13, no. 2, p. 155, Jan. 2022, doi: 10.3390/mi13020155.
  18. J. A. Kim, S. Hong, and W. J. Rhee, “Microfluidic three-dimensional cell culture of stem cells for high-throughput analysis,” World Journal of Stem Cells, vol. 11, no. 10, pp. 803–816, Oct. 2019, doi: 10.4252/wjsc.v11.i10.803.
  19. Totaro et al., “Downscaling screening cultures in a multifunctional bioreactor array‐on‐a‐chip for speeding up optimization of yeast‐based lactic acid bioproduction,” Biotechnology and Bioengineering, vol. 117, no. 7, pp. 2046–2057, Apr. 2020, doi: 10.1002/bit.27338.
  20. J. Sia, R. W. Sun, J. Chu, and S. Li, “Dynamic culture improves cell reprogramming efficiency,” Biomaterials, vol. 92, pp. 36–45, Jun. 2016, doi: 10.1016/j.biomaterials.2016.03.033.
  21. F. Zhang, D. Lin, S. Rajasekar, A. Sotra, and B. Zhang, “Pump‐Less platform enables Long‐Term recirculating perfusion of 3D printed tubular tissues,” Advanced Healthcare Materials, vol. 12, no. 27, Sep. 2023, doi: 10.1002/adhm.202300423.
  22. Rana, S. Kumar, T. J. Webster, and M. Ramalingam, “Impact of induced pluripotent stem cells in bone repair and regeneration,” Current Osteoporosis Reports, vol. 17, no. 4, pp. 226–234, Jun. 2019, doi: 10.1007/s11914-019-00519-9.
  23. P. Seib, M. Prewitz, C. Werner, and M. Bornhäuser, “Matrix elasticity regulates the secretory profile of human bone marrow-derived multipotent mesenchymal stromal cells (MSCs),” Biochemical and Biophysical Research Communications, vol. 389, no. 4, pp. 663–667, Nov. 2009, doi: 10.1016/j.bbrc.2009.09.051.
  24. M. P. Nikolova and M. Chavali, “Recent advances in biomaterials for 3D scaffolds: A review,” Bioactive Materials, vol. 4, pp. 271–292, Dec. 2019, doi: 10.1016/j.bioactmat.2019.10.005.
  25. X. Li, Y. Sun, L. Liao, and X. Su, “Response of mesenchymal stem cells to surface topography of scaffolds and the underlying mechanisms,” Journal of Materials Chemistry B, vol. 11, no. 12, pp. 2550–2567, Jan. 2023, doi: 10.1039/d2tb01875f.
  26. B. K. K. Teo, S. Ankam, L. Y. Chan, and E. K. F. Yim, “Nanotopography/Mechanical induction of Stem-Cell differentiation,” in Methods in Cell Biology, 2010, pp. 241–294. doi: 10.1016/s0091-679x(10)98011-4.
  27. Y.-C. Chen et al., “The effect of ultra-nanocrystalline diamond films on the proliferation and differentiation of neural stem cells,” Biomaterials, vol. 30, no. 20, pp. 3428–3435, Jul. 2009, doi: 10.1016/j.biomaterials.2009.03.058.
  28. K. Kulangara et al., “The effect of substrate topography on direct reprogramming of fibroblasts to induced neurons,” Biomaterials, vol. 35, no. 20, pp. 5327–5336, Jul. 2014, doi: 10.1016/j.biomaterials.2014.03.034.
  29. Samba, R. Hernández, N. Rescignano, C. Mijangos, and J. M. Kenny, “Nanocomposite hydrogels based on embedded PLGA nanoparticles in gelatin,” Nanocomposites, vol. 1, no. 1, pp. 46–50, Jan. 2015, doi: 10.1179/2055033214y.0000000006.
  30. S. Battista et al., “The effect of matrix composition of 3D constructs on embryonic stem cell differentiation,” Biomaterials, vol. 26, no. 31, pp. 6194–6207, Nov. 2005, doi: 10.1016/j.biomaterials.2005.04.003.
  31. M. Akhmanova, E. O. Osidak, S. P. Domogatsky, S. Rodin, and A. Domogatskaya, “Physical, spatial, and molecular aspects of extracellular matrix ofIN VivoNiches and artificial scaffolds relevant to stem cells research,” Stem Cells International, vol. 2015, pp. 1–35, Jan. 2015, doi: 10.1155/2015/167025.
  32. M. Akbarian, K. Ali, S. Eghbalpour, and V. N. Uversky, “Bioactive peptides: synthesis, sources, applications, and proposed mechanisms of action,” International Journal of Molecular Sciences, vol. 23, no. 3, p. 1445, Jan. 2022, doi: 10.3390/ijms23031445.
  33. S. M. Willerth, A. Rader, and S. E. Sakiyama‐Elbert, “The effect of controlled growth factor delivery on embryonic stem cell differentiation inside fibrin scaffolds,” Stem Cell Research, vol. 1, no. 3, pp. 205–218, Sep. 2008, doi: 10.1016/j.scr.2008.05.006.
  34. M. I. Dishowitz, F. Zhu, H. G. Sundararaghavan, J. L. Ifkovits, J. A. Burdick, and K. D. Hankenson, “Jagged1 immobilization to an osteoconductive polymer activates the Notch signaling pathway and induces osteogenesis,” Journal of Biomedical Materials Research Part A, vol. 102, no. 5, pp. 1558–1567, Jul. 2013, doi: 10.1002/jbm.a.34825.
  35. L. E. Wazan, D. Urrutia-Cabrera, and R. C.-B. Wong, “Using transcription factors for direct reprogramming of neurons in vitro,” World Journal of Stem Cells, vol. 11, no. 7, pp. 431–444, Jul. 2019, doi: 10.4252/wjsc.v11.i7.431.
  36. N. Cao et al., “Conversion of human fibroblasts into functional cardiomyocytes by small molecules,” Science, vol. 352, no. 6290, pp. 1216–1220, Jun. 2016, doi: 10.1126/science.aaf1502.
  37. X. Zhao et al., “Enhanced gene delivery by chitosan-disulfide-conjugated LMW-PEI for facilitating osteogenic differentiation,” Acta Biomaterialia, vol. 9, no. 5, pp. 6694–6703, May 2013, doi: 10.1016/j.actbio.2013.01.039.
  38. H. Liu et al., “Emerging landscape of cell penetrating peptide in reprogramming and gene editing,” Journal of Controlled Release, vol. 226, pp. 124–137, Mar. 2016, doi: 10.1016/j.jconrel.2016.02.002.
  39. Md. K. J. Rafi, S. Singh, V. Kanchan, C. Anish, and A. K. Panda, “Controlled release of bioactive recombinant human growth hormone from PLGA microparticles,” Journal of Microencapsulation, vol. 27, no. 6, pp. 552–560, Aug. 2010, doi: 10.3109/02652048.2010.489974.
  40. P. Sivashankari and M. Prabaharan, “Prospects of chitosan-based scaffolds for growth factor release in tissue engineering,” International Journal of Biological Macromolecules, vol. 93, pp. 1382–1389, Dec. 2016, doi: 10.1016/j.ijbiomac.2016.02.043.
CRediT Author Statement

The author reviewed the results and approved the final version of the manuscript.

Acknowledgements

We would like to thank Reviewers for taking the time and effort necessary to review the manuscript. We sincerely appreciate all valuable comments and suggestions, which helped us to improve the quality of the manuscript.

Funding

No funding was received to assist with the preparation of this manuscript.

Ethics Declarations

Conflict of interest

The authors have no conflicts of interest to declare that are relevant to the content of this article.

Availability of Data and Materials

Data sharing is not applicable to this article as no new data were created or analysed in this study.

Author Information

Contributions

All authors have equal contribution in the paper and all authors have read and agreed to the published version of the manuscript.

Corresponding Author



Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution NoDerivs is a more restrictive license. It allows you to redistribute the material commercially or non-commercially but the user cannot make any changes whatsoever to the original, i.e. no derivatives of the original work. To view a copy of this license, visit: https://creativecommons.org/licenses/by-nc-nd/4.0/

Cite this Article

Na Zeng, “The Impact of Cellular Microenvironments and Biomaterials on Induced Pluripotent Stem Cell Generation”, Journal of Smart and Sustainable Farming, pp. 119-130, 30 July 2025, doi: 10.64026/JSSF/2025012.

Copyright

© 2025 Na Zeng. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Journals
JCCN JDBIM JSSF
Policies
Publication Ethics Copyright Policy Open Access Policy Article Posting Policy Advertising Policy Privacy Policy Data Availability Policy
Ethics
Conflicts of interest/Competing interests Allegations of Misconduct Appeals Process Complaints Process Peer Review Process Authorship Criteria Terms and Conditions
Resources
Ansis Manager Contact Us
Information
Authors Editors Librarians Societies Journal News
© Ansis Publications, All Right Reserved. Designed By Ansis Publications
Home About Us Resource Contact