Magnetic bioassembly platforms for establishing craniofacial exocrine gland organoids as aging in vitro models

PLoS One. 2022 Aug 5;17(8):e0272644. doi: 10.1371/journal.pone.0272644. eCollection 2022.

Abstract

A multitude of aging-related factors and systemic conditions can cause lacrimal gland (LG) or salivary gland (SG) hypofunction leading to degenerative dry eye disease (DED) or dry mouth syndrome, respectively. Currently, there are no effective regenerative therapies that can fully reverse such gland hypofunction due to the lack of reproducible in vitro aging models or organoids required to develop novel treatments for multi-omic profiling. Previously, our research group successful developed three-dimensional (3D) bioassembly nanotechnologies towards the generation of functional exocrine gland organoids via magnetic 3D bioprinting platforms (M3DB). To meet the needs of our aging Asian societies, a next step was taken to design consistent M3DB protocols to engineer LG and SG organoid models with aging molecular and pathological features. Herein, a feasible step-by-step protocol was provided for producing both LG and SG organoids using M3DB platforms. Such protocol provided reproducible outcomes with final organoid products resembling LG or SG native parenchymal epithelial tissues. Both acinar and ductal epithelial compartments were prominent (21 ± 4.32% versus 42 ± 6.72%, respectively), and could be clearly identified in these organoids. Meanwhile, these can be further developed into aging signature models by inducing cellular senescence via chemical mutagenesis. The generation of senescence-like organoids will be our ultimate milestone aiming towards high throughput applications for drug screening and discovery, and for gene therapy investigations to reverse aging.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bioprinting* / methods
  • Magnetic Phenomena
  • Organoids*
  • Salivary Glands

Grants and funding

This research is funded by Thailand Science Research and Innovation Fund Chulalongkorn University (Grant number: CU_FRB65_hea (7)_013_32_08) to JNF and AM. This project is funded by the National Research Council of Thailand (NRCT), by a Mid-career Research Grant (Grant number: NRCT5-RSA63001-12) to JNF. Avatar Biotechnologies for Oral Health and Healthy Longevity Research Unit is funded by the Ratchadaphiseksomphot Endowment Fund, Chulalongkorn University (Grant number: 33/2565 : RU). TR is supported by a Postdoctoral Fellowship, Ratchadapisek Somphot Fund, Chulalongkorn University. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.