Novel Mesenchymal Stem Cell Spheroids with Enhanced Stem Cell Characteristics and Bone Regeneration Ability

被引：17

作者：

Ohori-Morita, Yumi ^{[1
]}

Niibe, Kunimichi ^{[1
]}

Limraksasin, Phoonsuk ^{[1
]}

Nattasit, Praphawi ^{[1
]}

Miao, Xinchao ^{[1
]}

Yamada, Masahiro ^{[1
]}

Mabuchi, Yo ^{[2
]}

Matsuzaki, Yumi ^{[3
]}

Egusa, Hiroshi ^{[1
,4
]}

机构：

[1] Tohoku Univ, Div Mol & Regenerat Prosthodont, Grad Sch Dent, Aoba Ku, 4-1 Seiryo Machi, Sendai, Miyagi 9808575, Japan

[2] Tokyo Med & Dent Univ, Grad Sch Med & Dent Sci, Dept Biochem & Biophys, Bunkyo Ku, 1-5-45 Yushima, Tokyo 1138510, Japan

[3] Shimane Univ, Fac Med, Dept Life Sci, 89-1 Enya Cho, Izumo, Shimane 6938501, Japan

[4] Tohoku Univ, Ctr Adv Stem Cell & Regenerat Res, Grad Sch Dent, Sendai, Miyagi 9808575, Japan

来源：

STEM CELLS TRANSLATIONAL MEDICINE | 2022年 / 11卷 / 04期

基金：

日本学术振兴会;

关键词：

bone regeneration; immunomodulatory ability; mesenchymal stem cells; neurosphere culture medium; shaking culture; STROMAL CELLS; EXTRACELLULAR-MATRIX; CULTURE; DIFFERENTIATION; PROLIFERATION; PHENOTYPES; CAPACITY; HYPOXIA; SOX2;

D O I：

10.1093/stcltm/szab030

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

Mesenchymal stem cells (MSCs) exhibit self-renewal, multi-lineage differentiation potential and immunomodulatory properties, and are promising candidates for cellular therapy of various tissues. Despite the effective function of MSCs, the gradual loss of stem cell characteristics that occurs with repeated passages may significantly limit their therapeutic potential. A novel 3D shaking method was previously established to generate MSC spheroids in growth medium (GM-spheroids) and successfully maintain the multipotency of expanded MSCs, yet the expression of MSC-related genes was still low. In this study, we used a neurosphere culture technique to optimize the shaking culture method using human bone marrow-derived MSCs (BM-MSCs). MSC spheroids generated in neurosphere medium (NM-spheroids) maintained high expression of MSC-related genes during 3 weeks of prolonged shaking culture. Moreover, NM-spheroids generated from expanded MSCs showed high viability, upregulation of MSC-related and immune-related genes, and recovery of differentiation potential in vitro. Expanded adherent MSCs, GM-spheroids, and NM-spheroids were transplanted into a rat femur bone defect model to investigate their therapeutic potential in bone repair. Adherent MSCs and GM-spheroids showed delayed bone healing. In contrast, NM-spheroids showed high transplantation efficiency and enhanced bone regeneration. These data suggest that NM-spheroids generated using modified neurosphere culture conditions under continuous shaking recovered their stem cell characteristics in vitro and enhanced bone regeneration in vivo. Therefore, NM-spheroids should have great clinical potential for bone and tissue regenerative therapies as a stem cell-based biomaterial therapy.

引用

页码：434 / 449

页数：16

共 67 条

[1] Sphere-Derived Multipotent Progenitor Cells Obtained From Human Oral Mucosa Are Enriched in Neural Crest Cells [J].