期刊论文详细信息
Head & Face Medicine
First-in-human study and clinical case reports of the alveolar bone regeneration with the secretome from human mesenchymal stem cells
Hideharu Hibi1  Takamasa Kawai1  Masashi Osugi1  Wataru Katagiri1 
[1] Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya 466-8550, Japan
关键词: Bone;    Regenerative medicine;    Tissue engineering;    Mesenchymal stem cells (MSC);    Secretome;   
Others  :  1235401
DOI  :  10.1186/s13005-016-0101-5
 received in 2015-06-25, accepted in 2016-01-12,  发布年份 2016
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【 摘 要 】

Background

Secreted growth factors and cytokines in the conditioned medium from bone marrow-derived mesenchymal stem cells (MSC-CM) have several effects on cell behavior. Our previous studies revealed that MSC-CM enhances bone regeneration by increasing cell mobilization, angiogenesis, and osteogenesis in vitro and in vivo. This clinical study was undertaken to evaluate the safety and use of MSC-CM for alveolar bone regeneration in eight patients who were diagnosed as needing bone augmentation prior to dental implant placement.

Methods

The protocol of this clinical study was approved by the ethics committee of Nagoya University Hospital. MSC-CM was prepared from conditioned medium from commercially available human bone marrow-derived MSCs. Patients were treated with beta-tricalcuim phosphate (β-TCP) or an atelocollagen sponge soaked with MSC-CM. Clinical and radiographic assessments were performed during the follow-up period. Histological assessments were also performed in some cases. Clinical and histological data from patients who underwent the SFE procedure without MSC-CM were also used retrospectively as reference controls.

Results

MSC-CM contained several cytokines such as insulin-like growth factor-1, vascular endothelial growth factor, transforming growth factor-β1, and hepatocyte growth factor in relatively low amounts. No systemic or local complications were reported throughout the study. Radiographic evaluation revealed early bone formation in all cases. Histological evaluation also supported the radiographic findings. Furthermore, infiltration of inflammatory cells was scarce throughout the specimens.

Conclusions

MSC-CM was used safely and with less inflammatory signs and appears to have great osteogenic potential for regenerative medicine of bone. This is the first in-human clinical study of alveolar bone regeneration using MSC-CM.

【 授权许可】

   
2016 Katagiri et al.

【 预 览 】
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20160120095300851.pdf 1690KB PDF download
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20150407095712500.pdf 165KB PDF download
Fig. 1. 29KB Image download
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【 参考文献 】
  • [1]Arrington ED, Smith WJ, Chambers HG, Bucknell AL, Davino NA. Complications of iliac crest bone graft harvesting. Clin Orthop Relat Res. 1996; 329:300-309.
  • [2]Joshi A, Kostakis GC. An investigation of post-operative morbidity following iliac crest graft harvesting. Br Dent J. 2004; 196:167-171.
  • [3]Damien CJ, Parsons JR. Bone graft and bone graft substitutes: a review of current technology and applications. J Appl Biomater. 1991; 2:187-208.
  • [4]Herford AS, Boyne PJ. Reconstruction of mandibular continuity defects with bone morphogenic protein-2 (rhBMP-2). J Oral Maxillofac Surg. 2008; 66:616-624.
  • [5]Woo EJ. Adverse events reported after the use of recomninant human bone morphogenetic protein 2. J Oral Maxillofac Surg. 2012; 70:765-767.
  • [6]Perri B, Cooper M, Lauryssen C, Anand N. Adverse swelling associated with use of rh-BMP-2 in anterior cervical discectomy and fusion: a case study. Spine J. 2007; 7:235-239.
  • [7]Vaidya R, Carp J, Sethi A, Bartol S, Craig J, Les CM. Complications of anterior cervical discectomy and fusion using recombinant human bone morphogenetic protein-2. Eur Spine J. 2007; 16:1257-1265.
  • [8]Kawasaki K, Aihara M, Honmo J, Sakurai S, Fujimaki Y, Sakamoto K et al.. Effects of reconmbinant human bone morphogenetic protein-2 on differentiation of cells isolated from human bone, muscle, and skin. Bone. 1998; 23:223-231.
  • [9]Langer R, Vacanti JP. Tissue engineering. Science. 1993; 260:920-926.
  • [10]Yamada Y, Ueda M, Naiki T, Takahashi M, Hata K, Nagasaka T. Autogenous injectable bone for regeneration with mesenchymal stem cells (MSCs) and platelet-rich plasma (PRP) – Tissue-engineered bone regeneration. Tissue Eng. 2004; 10:955-964.
  • [11]Yamada Y, Nakamura S, Ito K, Umemura E, Hara K, Nagasaka T et al.. Injectable bonetissue engineeringusingexpanded mesenchymal stem cells. Stem Cells. 2013; 31:572-580.
  • [12]Muller-Ehmsen J, Whittaker P, Kloner RA, Dow JS, Sakoda T, Long TI et al.. Survival and development of neonatal rat cardiomyocytes transplanted into adult myocardium. J Mol Cell Cardiol. 2002; 34:107-116.
  • [13]Toma C, Wagner WR, Bowry S, Schwartz A, Villanueva F. Fate of culture-expanded mesenchymal stem cells in the microvasculature: in vivo observations of cell kinetics. Circ Res. 2009; 104:398-402.
  • [14]Ide C, Nakai Y, Nakano N, Seo T, Yamada Y, Endo K et al.. Bone marrow stromal cell transplantation for treatment of sub-acute spinal cord injury in rat. Brain Res. 2010; 1332:32-47.
  • [15]Chen L, Tredget EE, Wu PYG, Wu Y. Paracrine factors of mesenchymal stem cells recruit macrophages and endothelial lineage cells and enhance wound healing. PLoS One. 2008; 3:e1886.
  • [16]Ciapetti G, Granchi D, Baldini N. The combined use of mesenchymal stromal cells and scaf- folds for bone repair. Curr Pharm Des. 2012; 18:1796-1820.
  • [17]Baglio SL, Pegtel DM, Baldini N. Mesenchymal stem cell secreted vesicles provide novel opportunities in (stem) cell-free therapy. Front Physiol. 2012; 3:1-11.
  • [18]Katagiri W, Osugi M, Kawai T, Ueda M. Novel cell-free regenerative medicine of bone using stem cell derived factors. Int J Oral Maxillofac Implants. 2013; 28:1009-1016.
  • [19]Osugi M, Katagiri W, Yoshimi R, Inukai T, Hibi H, Ueda M. Conditioned media from mesenchymal stem cells enhancedbone regeneration in rat calvarial bone defects. Tissue Eng Part A. 2012; 18:14779-1489.
  • [20]Inukai T, Katagiri W, Yoshimi R, Osugi M, Kawai T, Hibi H et al.. Novel application of stem cell-derived factors for periodontal regeneration. Biochem Biophys Res Commun. 2013; 430:763-768.
  • [21]Kawai T, Katagiri W, Osugi M, Sugimura Y, Hibi H, Ueda M. Secretomes from bone marrow-derived mesenchymal stromal cells enhance periodontal tissue regeneration. Cytotherapy. 2015; 17:369-381.
  • [22]Tatum H. Maxillary and sinus implant reconstructions. Dent Clin North Am. 1986; 30:207-229.
  • [23]Okuda K, Yamamiya K, Kawase T, Mizuno H, Ueda M, Yoshie H. Treatment of human infrabony periodontal defects by grafting human cultured periosteum sheets combined with platelet-rich plasma and porus hydroxyapatite granules: case series. J Int Acad Periodontol. 2009; 11:206-213.
  • [24]Freyman T, Polin G, Osman H, Crary J, Lu M, Cheng L et al.. A quantitative, randomized study evaluating three methods of mes- enchymal stem cell delivery fol- lowing myocardial infarction. Eur Heart J. 2006; 27:1114-1122.
  • [25]Parekkadan B, van Poll D, Suganuma K, Carter EA, Berthiaume F, Tilles AW et al.. Mesenchymal stem cell-derived molecules reverse fulminant hepatic failure. PLoS One. 2007; 2:e941.
  • [26]Lee JK, Jin HK, Endo S, Schuchman EH, Carter JE, Bae JS. Intracerebral trans- plantation of bone marrow-derived mesenchymal stem cells reduces amyloid-beta deposition and res- cues memory deficits in Alzheimer’s disease mice by modulation of immune responses. Stem Cells. 2010; 28:329-343.
  • [27]Cornish J, Grey A, Callon KE, Naot D, Hill BL, Lin CQ et al.. Shared pathways of osteoblast mitogenesis induced by amylin, adrenomedullin, and IGF-1. Biochem Biophys Res Commun. 2004; 318:240-246.
  • [28]Li Y, Yu X, Lin S, Li X, Zhang S, Song YH. Insulin-like growth factor 1 enhances the migratory capacity of mesenchymal stem cells. Biochem Biophys Res Commun. 2007; 356:780-784.
  • [29]Han X, Amar S. Role of insulin-like growth factor-1 signaling in dental fibroblast apoptosis. J Periodontol. 2003; 74:1176-1182.
  • [30]Kaiglar D, Krebsbach PH, West ER, Horger K, Huang YC, Mooney DJ. Endothelial cell modulation of bone marrow stromal cell osteogenic potential. FASEB J. 2005; 19:665-667.
  • [31]Bostrom MP, Asnis P. Transforming growth factor beta in fracture repair. Clin Orthop Relat Res. 1998; 355:S124-131.
  • [32]Fujita T, Shiba H, van Dyke TE, Kurihara H. Differential effects of growth factors and cytokines on the synthesis of SPARC, DNA, fibronectin and alkaline phosphatase activity in human periodontal ligament cells. Cell Biol Int. 2004; 28:281-286.
  • [33]Gao J, Symons AL, Bartold PM. Expression of transforming growth factor-beta 1 (TGF-beta1) in the developing periodontium of rats. J Dent Res. 1998; 77:1708-1716.
  • [34]Morishita R, Nakamura S, Hayashi S, Taniyama Y, Moriguchi A, Nagono T et al.. Therapeutic angiogenesis induced by human recombinant hepatocyte growth factor in rabbit hind limb ischemia model as cytokine supplement therapy. Hypertension. 1999; 33:1379-1384.
  • [35]Ozaki Y, Nishimura M, Sekiya K, Suehiro F, Kanawa M, Nikawa H et al.. Comprehensive analysis of chemotactic factors for bone marrow mesenchymal stem cells. Stem Cells Dev. 2007; 16:119-129.
  • [36]Chen L, Jiang W, Huang J, He B, Zuo G, Zhang W et al.. Insulin-like growth factor 2 (IGF-2) potentiates BMP-9-induced osteogenic differentiation and bone formation. J Bone Miner Res. 2010; 25:2447-2459.
  • [37]Cowan CM, Aghaloo T, Chou YF, Walder B, Zhang X, Soo C et al.. MicroCT evaluation of three-dimensional mineralization in response to BMP-2 doses in vitro and in critical sized rat calvarial defects. Tissue Eng. 2007; 13:501-512.
  • [38]Ionescu L, Byrne RN, van Haaften T, Vadivel A, Alphonse RS, Rey-Parra GJ et al.. Stem cell conditioned medium improves acute lung injury in mice: in vivo evidence for stem cell paracrine action. Am J Physiol Lung Cell Mol Physiol. 2012; 303:L967-977.
  • [39]Zerbo IR, Zijderveld SA, De Boer A, Bronckers ALJJ, De Lange G, Bruggenkate CMT et al.. Histomorphometry of human sinus floor augmentation using a porous β-tricalcium phosphate: a prospective study. Clin Oral Implants Res. 2004; 15:724-732.
  • [40]Badylak SF, Valentin JE, Ravindra AK, McCabe GP, Stewart-Akers AM. Macrophage phenotype as a determinant of biologic scaffold remodeling. Tissue Eng Part A. 2008; 14:1835-1842.
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