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Tissue Specific Extracellular Matrix Extract Promotes Salivary Gland Organoid Formation with Human Salivary Progenitors

23 Pages Posted: 30 Jan 2019 First Look: Preprint

See all articles by Zhang Siqi

Zhang Siqi

Peking University - Central Laboratory; Peking University - Department of Oral and Maxillofacial Surgery; Peking University - Laboratory of Biomaterials and Regenerative Medicine

Sui Yi

Peking University - Central Laboratory; Peking University - Department of Oral and Maxillofacial Surgery

Fu Xiaoming

Peking University - Central Laboratory; Peking University - Department of Oral and Maxillofacial Surgery

Feng Yanrui

Peking University - Central Laboratory; Peking University - Department of Oral and Maxillofacial Surgery

Luo Zuyuan

Peking University - Laboratory of Biomaterials and Regenerative Medicine

Wei Shicheng

Peking University - Central Laboratory; Peking University - Department of Oral and Maxillofacial Surgery; Peking University - Laboratory of Biomaterials and Regenerative Medicine

Zhang Yuanyuan

Wake Forest University - Institute for Regenerative Medicine

Abstract

Hypofunction of the salivary glands (SGs) has several detrimental effects. Several approaches can be used to restore the function of damaged SGs, such as tissue engineering based on stem cells and biomaterials. Among these, three dimensional (3D) culture without biomaterials (termed organoids) can recapitulate the characteristics of the native organ in vivo. However, despite the substantial progress made, most organoids which are formed from stem cells or cell aggregates still lack a specific tissue niche. We hypothesized that tissue specific ECM proteins are required for formation and maintenance of functional organoids. Thus, we evaluate the effect of human tissue specific ECM extracts on the formation of functional SG organoids containing human SG epithelial and mesenchymal cells. We prepared human salivary gland ECM (hSG-ECM) with a growth factor-enriched supplement and the prepared hSG-ECM was introdeced in a uniform high-throughput 3D platform. First, we determined the optimum culture conditions; organoids comprising 5,000 cells at a mesenchymal: epithelial cell ratio of 1:9 exhibited a low frequency of apoptosis, high proliferation capacity, and a structure resembling that of SGs. Introduction of hSG-ECM extract with proper concentration resulted in maintenance of the stem cell niche and promotion of stem cell differentiation. Moreover, treatment of the organoids with decellularized supplements increased their sensitivity to neurotransmitters. In conclusion, we developed functional human SG organoids using salivary progenitors and ECM extract. The SG organoids have potential for SG tissue repair, drug development, and disease modeling.

Keywords: Human salivary gland, Extracellular matrix, Organoids, Stem/Progenitor cell(s), Regenerative medicine

Suggested Citation

Siqi, Zhang and Yi, Sui and Xiaoming, Fu and Yanrui, Feng and Zuyuan, Luo and Shicheng, Wei and Yuanyuan, Zhang, Tissue Specific Extracellular Matrix Extract Promotes Salivary Gland Organoid Formation with Human Salivary Progenitors (January 29, 2019). Available at SSRN: https://ssrn.com/abstract=3325396

Zhang Siqi

Peking University - Central Laboratory ( email )

38 Xueyuan Rd
Haidian District
Beijing, 100191
China

Peking University - Department of Oral and Maxillofacial Surgery ( email )

38 Xueyuan Rd
Haidian District
Beijing, 100191
China

Peking University - Laboratory of Biomaterials and Regenerative Medicine ( email )

Beijing, 100871
China

Sui Yi

Peking University - Central Laboratory

38 Xueyuan Rd
Haidian District
Beijing, 100191
China

Peking University - Department of Oral and Maxillofacial Surgery

38 Xueyuan Rd
Haidian District
Beijing, 100191
China

Fu Xiaoming

Peking University - Central Laboratory

38 Xueyuan Rd
Haidian District
Beijing, 100191
China

Peking University - Department of Oral and Maxillofacial Surgery

38 Xueyuan Rd
Haidian District
Beijing, 100191
China

Feng Yanrui

Peking University - Central Laboratory

38 Xueyuan Rd
Haidian District
Beijing, 100191
China

Peking University - Department of Oral and Maxillofacial Surgery

38 Xueyuan Rd
Haidian District
Beijing, 100191
China

Luo Zuyuan

Peking University - Laboratory of Biomaterials and Regenerative Medicine

Beijing, 100871
China

Wei Shicheng

Peking University - Central Laboratory

38 Xueyuan Rd
Haidian District
Beijing, 100191
China

Peking University - Department of Oral and Maxillofacial Surgery

38 Xueyuan Rd
Haidian District
Beijing, 100191
China

Peking University - Laboratory of Biomaterials and Regenerative Medicine

Beijing, 100871
China

Zhang Yuanyuan (Contact Author)

Wake Forest University - Institute for Regenerative Medicine

391 Technology Way
Winston-Salem, NC
United States

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