Laminin-Augmented Decellularized Extracellular Matrix Ameliorating Neural Differentiation and Neuroinflammation in Human Mini-Brains

  • Small. 2023 Dec 31:e2308815. doi: 10.1002/smll.202308815.
Mihyeon Bae  1 ,  Huyen Ngo  2 ,  You Jung Kang  2 ,  Su-Jin Lee  3 ,  Wonbin Park  1 ,  Yeonggwon Jo  4 ,  Yoo-Mi Choi  5 ,  Joeng Ju Kim  1 ,  Hee-Gyeong Yi  6 ,  Hyung-Seok Kim  7 ,  Jinah Jang  1  4  8 ,  Dong-Woo Cho  1 ,  Hansang Cho  2
Affiliations
  • 1. Department of Mechanical Engineering, Pohang University of Science and Technology (POSTECH), Pohang, Kyungbuk, 37673, South Korea.
  • 2. Department of Biophysics, Institute of Quantum Biophysics, Department of Intelligent Precision Healthcare Convergence, Sungkyunkwan University, Suwon, Gyeonggi, 16419, South Korea.
  • 3. Biomedical Research Institute, Chonnam National University Hospital, Gwangju, 61469, South Korea.
  • 4. School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology (POSTECH), Pohang, Kyungbuk, 37673, South Korea.
  • 5. Department of Convergence IT Engineering, Pohang University of Science and Technology (POSTECH), Pohang, Kyungbuk, 37673, South Korea.
  • 6. Department of Convergence Biosystems Engineering, College of Agriculture and Life Sciences, Chonnam National University, Gwangju, 61186, South Korea.
  • 7. Department of Forensic medicine, Chonnam National University Medical School & Research Institute of Medical Sciences, Gwangju, 61469, South Korea.
  • 8. Institute for Convergence Research and Education in Advanced Technology, Yonsei University, Seoul, 03722, Republic of Korea.
PMID: 38161254 DOI: 10.1002/smll.202308815
Abstract

Non-neural extracellular matrix (ECM) has limited application in humanized physiological neural modeling due to insufficient brain-specificity and safety concerns. Although brain-derived ECM contains enriched neural components, certain essential components are partially lost during the decellularization process, necessitating augmentation. Here, it is demonstrated that the laminin-augmented porcine brain-decellularized ECM (P-BdECM) is xenogeneic factor-depleted as well as favorable for the regulation of human neurons, astrocytes, and microglia. P-BdECM composition is comparable to human BdECM regarding brain-specificity through the matrisome and gene ontology-biological process analysis. As augmenting strategy, laminin 111 supplement promotes neural function by synergic effect with laminin 521 in P-BdECM. Annexin A1(ANXA1) and Peroxiredoxin(PRDX) in P-BdECM stabilized microglial and astrocytic behavior under normal while promoting active neuroinflammation in response to neuropathological factors. Further, supplementation of the brain-specific molecule to non-neural matrix also ameliorated glial cell inflammation as in P-BdECM. In conclusion, P-BdECM-augmentation strategy can be used to recapitulate humanized pathophysiological cerebral environments for neurological study.

Keywords
cerebral decellularized extracellular matrix; laminin; neural differentiation; neuroinflammation.
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