Souza Alann Thaffarell Portilho, Freitas Gileade Pereira, Lopes Helena Bacha, Weffort Denise, Adolpho Leticia Faustino, Gomes Maria Paula Oliveira, Oliveira Fabiola Singaretti, Almeida Adriana Luisa Gonçalves, Beloti Marcio Mateus, Rosa Adalberto Luiz
Bone Research Lab, Ribeirão Preto School of Dentistry, University of São Paulo, Ribeirão Preto 14040-904, SP, Brazil; Centro Universitário Metropolitano da Amazônia, Belém 66053-000, PA, Brazil.
Bone Research Lab, Ribeirão Preto School of Dentistry, University of São Paulo, Ribeirão Preto 14040-904, SP, Brazil.
Life Sci. 2024 Mar 1;340:122463. doi: 10.1016/j.lfs.2024.122463. Epub 2024 Jan 28.
Cell therapy utilizing mesenchymal stem cells (MSCs) from healthy donors (HE-MSCs) is a promising strategy for treating osteoporotic bone defects. This study investigated the effects of interaction between HE-MSCs and MSCs from osteoporotic donors (ORX-MSCs) on osteoblast differentiation of MSCs and of HE-MSCs on bone formation in calvarial defects of osteoporotic rats.
Osteoporosis was induced by orchiectomy (ORX) and its effects on the bone were evaluated by femur microtomography (μCT) and osteoblast differentiation of bone marrow MSCs. HE- and ORX-MSCs were cocultured, and osteoblast differentiation was evaluated using genotypic and phenotypic parameters. HE-MSCs were injected into the calvarial defects of osteoporotic rats, and bone formation was evaluated by μCT, histology, and gene expression of osteoblast markers.
ORX-induced osteoporosis was revealed by reduced bone morphometric parameters and osteoblast differentiation in ORX-MSCs. HE-MSCs partially recovered the osteogenic potential of ORX-MSCs, whereas HE-MSCs were mildly affected by ORX-MSCs. Additionally, the bone morphogenetic protein and wingless-related integration site signaling pathway components were similarly modulated in cocultures involving ORX-MSCs. HE-MSCs induced meaningful bone formation, highlighting the effectiveness of cell therapy even in osteoporotic bones.
These results provide new perspectives on the development of cell-based therapies to regenerate bone defects in patients with disorders that affect bone tissue.
利用健康供体的间充质干细胞（HE-MSCs）进行细胞治疗是治疗骨质疏松性骨缺损的一种有前景的策略。本研究调查了HE-MSCs与骨质疏松供体的间充质干细胞（ORX-MSCs）之间的相互作用对MSCs成骨分化的影响，以及HE-MSCs对骨质疏松大鼠颅骨缺损骨形成的影响。
通过去势手术（ORX）诱导骨质疏松，并通过股骨显微CT（μCT）和骨髓间充质干细胞的成骨分化来评估其对骨骼的影响。将HE-MSCs和ORX-MSCs进行共培养，并使用基因型和表型参数评估成骨分化。将HE-MSCs注射到骨质疏松大鼠的颅骨缺损处，并通过μCT、组织学和成骨细胞标志物的基因表达来评估骨形成。
ORX诱导的骨质疏松表现为ORX-MSCs中骨形态计量学参数降低和成骨细胞分化减少。HE-MSCs部分恢复了ORX-MSCs的成骨潜能，而HE-MSCs受到ORX-MSCs的轻度影响。此外，在涉及ORX-MSCs的共培养中，骨形态发生蛋白和无翅相关整合位点信号通路成分受到类似的调节。HE-MSCs诱导了有意义的骨形成，突出了细胞治疗即使在骨质疏松骨中也具有有效性。
这些结果为开发基于细胞的疗法以再生影响骨组织的疾病患者的骨缺损提供了新的视角。
