1. Academic Validation
  2. Laminin-Augmented Decellularized Extracellular Matrix Ameliorating Neural Differentiation and Neuroinflammation in Human Mini-Brains

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

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.
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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