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Small, Dec 31 2023, | https://doi.org/10.1002/smll.202308815 Laminin-Augmented Decellularized Extracellular Matrix Ameliorating Neural Differentiation and Neuroinflammation in Human Mini-Brains

Mihyeon Bae ¹, Huyen Ngo ², You Jung Kang ², Su-Jin Lee³, 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

¹Department of Mechanical Engineering, Pohang University of Science and Technology (POSTECH), Pohang, Kyungbuk, 37673, South Korea.

²Department of Biophysics, Institute of Quantum Biophysics, Department of Intelligent Precision Healthcare Convergence, Sungkyunkwan University, Suwon, Gyeonggi, 16419, South Korea.

³Biomedical Research Institute, Chonnam National University Hospital, Gwangju, 61469, South Korea.

⁴School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology (POSTECH), Pohang, Kyungbuk, 37673, South Korea.

⁵Department of Convergence IT Engineering, Pohang University of Science and Technology (POSTECH), Pohang, Kyungbuk, 37673, South Korea.

⁶Department of Convergence Biosystems Engineering, College of Agriculture and Life Sciences, Chonnam National University, Gwangju, 61186, South Korea.

⁷Department of Forensic medicine, Chonnam National University Medical School & Research Institute of Medical Sciences, Gwangju, 61469, South Korea.

⁸Institute for Convergence Research and Education in Advanced Technology, Yonsei University, Seoul, 03722, Republic of Korea.

M.B., H.N. contributed equally to this work.

CORRESPONDING AUTHORS : Hyung-Seok Kim, Jinah Jang, Dong-Woo Cho, Hansang Cho

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.

논문정보

형식Research article
게재일2023년 12월 (BRIC 등록일 2024-01-03)
연구진국내 연구진
분야 바이오·의료융합 > 뇌인지과학

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