マウス大腿骨骨折モデルにおける 脱分化脂肪細胞 (DFAT) 移植による骨形成促進効果
四肢の骨折は治療法や手術方法が確立されているが，重度の外傷，広範囲な骨欠損では，適切な治療や手術を施行しても，骨の癒合が不十分となることが多い．近年，整形外科領域においても，幹細胞などを利用した再生医療が期待されている．脱分化脂肪細胞 (dedifferentiated fat cell: DFAT) は成熟脂肪細胞に由来する間葉系幹細胞に類似した多能性細胞である．本研究は，マウス大腿骨骨折モデルに対し，DFAT をペプチドハイドロゲルと共に骨折部位に移植し，骨形成促進効果を検討した．その結果，DFAT 移植により仮骨形成が促進され，骨折部周囲の骨量の増加が誘導されることが明らかとなった．DF...
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| Published in | 日大医学雑誌 Vol. 79; no. 5; pp. 265 - 273 |
|---|---|
| Main Authors | , , , , , , |
| Format | Journal Article |
| Language | Japanese |
| Published |
日本大学医学会
01.10.2020
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| Subjects | |
| Online Access | Get full text |
| ISSN | 0029-0424 1884-0779 |
| DOI | 10.4264/numa.79.5_265 |
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| Abstract | 四肢の骨折は治療法や手術方法が確立されているが，重度の外傷，広範囲な骨欠損では，適切な治療や手術を施行しても，骨の癒合が不十分となることが多い．近年，整形外科領域においても，幹細胞などを利用した再生医療が期待されている．脱分化脂肪細胞 (dedifferentiated fat cell: DFAT) は成熟脂肪細胞に由来する間葉系幹細胞に類似した多能性細胞である．本研究は，マウス大腿骨骨折モデルに対し，DFAT をペプチドハイドロゲルと共に骨折部位に移植し，骨形成促進効果を検討した．その結果，DFAT 移植により仮骨形成が促進され，骨折部周囲の骨量の増加が誘導されることが明らかとなった．DFAT は，難治性骨折に対する治療用細胞源として有望であることが示された． |
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| AbstractList | 四肢の骨折は治療法や手術方法が確立されているが，重度の外傷，広範囲な骨欠損では，適切な治療や手術を施行しても，骨の癒合が不十分となることが多い．近年，整形外科領域においても，幹細胞などを利用した再生医療が期待されている．脱分化脂肪細胞 (dedifferentiated fat cell: DFAT) は成熟脂肪細胞に由来する間葉系幹細胞に類似した多能性細胞である．本研究は，マウス大腿骨骨折モデルに対し，DFAT をペプチドハイドロゲルと共に骨折部位に移植し，骨形成促進効果を検討した．その結果，DFAT 移植により仮骨形成が促進され，骨折部周囲の骨量の増加が誘導されることが明らかとなった．DFAT は，難治性骨折に対する治療用細胞源として有望であることが示された． |
| Author | 新井, 嘉則 山田, 知裕 加野, 浩一郎 中西, 一義 風間, 智彦 松本, 太郎 徳橋, 泰明 |
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| References | Shen B, Mu JX, Pei FX. Relationship among bone mineraldensity, collagen composition, and biomechanical propertiesof callus in the healing of osteoporotic fracture. Chin J Traumatol 2007; 10: 360–365. Soucacos PN, Dailiana Z, Beris AE, et al. Vascularised bonegrafts for the management of non-union. Injury 2006; 37Suppl 1: S41–50. Hamada K, Hirose M, Yamashita T, et al. Spatial distributionof mineralized bone matrix produced by marrow mesenchymal stem cells in self-assembling peptide hydrogel scaffold. JBiomed Mater Res A 2008; 84: 128–136. Bonnarens F, Einhorn TA. Production of a standard closedfracture in laboratory animal bone. J Orthop Res 1984; 2: 97–101. Kumar S, Ponnazhagan S. Mobilization of bone marrow mesenchymal stem cells in vivo augments bone healing in a mousemodel of segmental bone defect. Bone 2012; 50: 1012–1018. Batista MA, Leivas TP, Rodrigues CJ, et al. Comparisonbetween the effects of platelet-rich plasma and bone marrow concentrate on defect consolidation in the rabbit tibia. Clinics(Sao Paulo) 2011; 66: 1787–1792. Matsumoto T, Kano K, Kondo D, et al. Mature adipocytederived dedifferentiated fat cells exhibit multilineage potential. J Cell Physiol 2008; 215: 210–222. Li YF, Luo E, Feng G, et al. Systemic treatment with strontium ranelate promotes tibial fracture healing in ovariectomized rats. Osteoporos Int 2010; 21: 1889–1897. Granero-Molto F, Myers TJ, Weis JA, et al. Mesenchymalstem cells expressing insulin-like growth factor-I (MSCIGF)promote fracture healing and restore new bone formation inIrs1 knockout mice: analyses of MSCIGF autocrine and paracrine regenerative effects. Stem Cells 2011; 29: 1537–1548. Sakuma T, Matsumoto T, Kano K, et al. Mature, adipocytederived, dedifferentiated fat cells can differentiate into smoothmuscle-like cells and contribute to bladder tissue regeneration.J Urol 2009; 182: 355–365. Sugihara H, Yonemitsu N, Miyabara S, et al. Primary culturesof unilocular fat cells: characteristics of growth in vitro andchanges in differentiation properties. Differentiation 1986; 31:42–49. Wang CJ, Huang KE, Sun YC, et al. VEGF modulates angiogenesis and osteogenesis in shockwave-promoted fracturehealing in rabbits. J Surg Res 2011; 171: 114–119. Kikuta S, Tanaka N, Kazama T, et al. Osteogenic effects of dedifferentiated fat cell transplantation in rabbit models of bonedefect and ovariectomy-induced osteoporosis. Tissue Eng PartA 2013; 19: 1792–1802. Undale A, Fraser D, Hefferan T, et al. Induction of fracturerepair by mesenchymal cells derived from human embryonicstem cells or bone marrow. J Orthop Res 2011; 29: 1804–1811. Thonhoff JR, Lou DI, Jordan PM, et al. Compatibility of human fetal neural stem cells with hydrogel biomaterials in vitro.Brain Res 2008; 1187: 42–51. |
| References_xml | – reference: Wang CJ, Huang KE, Sun YC, et al. VEGF modulates angiogenesis and osteogenesis in shockwave-promoted fracturehealing in rabbits. J Surg Res 2011; 171: 114–119. – reference: Granero-Molto F, Myers TJ, Weis JA, et al. Mesenchymalstem cells expressing insulin-like growth factor-I (MSCIGF)promote fracture healing and restore new bone formation inIrs1 knockout mice: analyses of MSCIGF autocrine and paracrine regenerative effects. Stem Cells 2011; 29: 1537–1548. – reference: Hamada K, Hirose M, Yamashita T, et al. Spatial distributionof mineralized bone matrix produced by marrow mesenchymal stem cells in self-assembling peptide hydrogel scaffold. JBiomed Mater Res A 2008; 84: 128–136. – reference: Undale A, Fraser D, Hefferan T, et al. Induction of fracturerepair by mesenchymal cells derived from human embryonicstem cells or bone marrow. J Orthop Res 2011; 29: 1804–1811. – reference: Soucacos PN, Dailiana Z, Beris AE, et al. Vascularised bonegrafts for the management of non-union. Injury 2006; 37Suppl 1: S41–50. – reference: Batista MA, Leivas TP, Rodrigues CJ, et al. Comparisonbetween the effects of platelet-rich plasma and bone marrow concentrate on defect consolidation in the rabbit tibia. Clinics(Sao Paulo) 2011; 66: 1787–1792. – reference: Sakuma T, Matsumoto T, Kano K, et al. Mature, adipocytederived, dedifferentiated fat cells can differentiate into smoothmuscle-like cells and contribute to bladder tissue regeneration.J Urol 2009; 182: 355–365. – reference: Thonhoff JR, Lou DI, Jordan PM, et al. Compatibility of human fetal neural stem cells with hydrogel biomaterials in vitro.Brain Res 2008; 1187: 42–51. – reference: Bonnarens F, Einhorn TA. Production of a standard closedfracture in laboratory animal bone. J Orthop Res 1984; 2: 97–101. – reference: Kumar S, Ponnazhagan S. Mobilization of bone marrow mesenchymal stem cells in vivo augments bone healing in a mousemodel of segmental bone defect. Bone 2012; 50: 1012–1018. – reference: Sugihara H, Yonemitsu N, Miyabara S, et al. Primary culturesof unilocular fat cells: characteristics of growth in vitro andchanges in differentiation properties. Differentiation 1986; 31:42–49. – reference: Li YF, Luo E, Feng G, et al. Systemic treatment with strontium ranelate promotes tibial fracture healing in ovariectomized rats. Osteoporos Int 2010; 21: 1889–1897. – reference: Matsumoto T, Kano K, Kondo D, et al. Mature adipocytederived dedifferentiated fat cells exhibit multilineage potential. J Cell Physiol 2008; 215: 210–222. – reference: Shen B, Mu JX, Pei FX. Relationship among bone mineraldensity, collagen composition, and biomechanical propertiesof callus in the healing of osteoporotic fracture. Chin J Traumatol 2007; 10: 360–365. – reference: Kikuta S, Tanaka N, Kazama T, et al. Osteogenic effects of dedifferentiated fat cell transplantation in rabbit models of bonedefect and ovariectomy-induced osteoporosis. Tissue Eng PartA 2013; 19: 1792–1802. |
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| Snippet | 四肢の骨折は治療法や手術方法が確立されているが，重度の外傷，広範囲な骨欠損では，適切な治療や手術を施行しても，骨の癒合が不十分となることが多い．近年，整形外科... |
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| SubjectTerms | 再生医療 細胞治療 脱分化脂肪細胞 骨折治療 |
| Title | マウス大腿骨骨折モデルにおける 脱分化脂肪細胞 (DFAT) 移植による骨形成促進効果 |
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