Effects of hypoxia on osteogenic differentiation of mesenchymal stromal cells used as a cell therapy for avascular necrosis of the femoral head

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• 作者：Gabriela Ciapetti¹ ; ^{gabriela.ciapetti@ior.it" class="auth_mail" title="E-mail the corresponding author} ; Donatella Granchi¹ ; Caterina Fotia¹ ; Lucia Savarino¹ ; Dante Dallari² ; Nicola Del Piccolo² ; Davide Maria Donati³ ; ⁴ ; Nicola Baldini¹ ; ⁴
• 关键词：avascular necrosis ; bone marrow stromal cells ; bone regeneration ; hypoxia
• 刊名：Cytotherapy
• 出版年：2016
• 出版时间：September 2016
• 年：2016
• 卷：18
• 期：9
• 页码：1087-1099
• 全文大小：1913 K

文摘

Avascular necrosis of the femoral head (AVN) occurs as common result of various conditions or develops as a primary entity, with a high freqency in young adults. Because of its tendency toward osteoarthritis requiring total hip arthroplasty, alternative treatments are being advocated, including cell therapy with mesenchymal stromal cells (MSCs). Because osteonecrotic bone is a severely hypoxic tissue, with a 1–3% oxygen tension, the survival and function of multipotent cells is questionable.

Methods

In this study, the proliferative, immunophenotypic and osteogenic properties of bone marrow (BM)-derived MSCs from a clinical series of patients with AVN were evaluated under in vitro conditions mimicking the hypoxic milieu of AVN to verify the rationale for cell therapy. MSCs retrieved from the iliac crest (BM-MSC) were isolated, expanded and induced to osteogenic differentiation under a 2% pO₂ atmosphere (hypoxia) in comparison with the standard 21% pO₂ (normoxia) that is routinely used in cell culture assays.

Results

Both proliferation and colony-forming ability were significantly enhanced in hypoxia-exposed BM-MSCs compared with BM-MSCs under normoxia. The expression of bone-related genes, including alkaline phosphatase, Type I collagen, and osteocalcin was significantly increased under hypoxia. Moreover, mineral deposition after osteogenic induction was not hampered, but in some cases even enhanced under low oxygen tension.

Conclusions

These findings support autologous cell therapy as an effective treatment to stimulate bone healing in the hypoxic microenvironment of AVN.