Recombinant human bone morphogenetic protein-7 enhances bone formation ability of jaw bone defect using human umbilical cord mesenchymal stem cells combined with nano-hydroxyapatite/collagen/poly(L-lactide)

2020 ◽  
Author(s):  
E Lingling ◽  
Helin Xin ◽  
Xing Wang ◽  
Tao Cheng ◽  
Shou Zhang ◽  
...  
Keyword(s):  
Bone Formation ◽  
Bone Morphogenetic Protein ◽  
Bone Defect ◽  
Human Umbilical Cord ◽  
Heterotopic Bone ◽  
Heterotopic Bone Formation ◽  
Jaw Bone ◽  
Morphogenetic Protein ◽  
Human Bone Morphogenetic Protein

Abstract Background: Human umbilical cord mesenchymal stem cells (hUC-MSCs) have been suggested as an alternative source of MSCs. However, the studies on its bone formation ability in oral maxillo-facial bone defect are rare. This study investigated the bone formation ability of recombinant human bone morphogenetic protein-7 (rhBMP-7)-induced hUC-MSCs combined with nano-hydroxyapatite/collagen/poly(L-lactide) (nHAC/PLA) in the back of nude mice and jaw bone defect of rabbit. Methods: The characteristics of hUC-MSCs were analyzed by plastic adherence, cell phenotype and multilineage differentiation potential. Cell proliferation was examined using a CCK-8 assay. Osteogenic differentiation was evaluated by quantitative calcium concentration, phosphorous concentration, alkaline phosphatase (ALP) activity, osteocalcin (OCN) concentration, mineral formation, and the mRNA levels of ALP, OCN and bone morphogenetic protein (BMP)-2. Scanning electron microscopy was used to observe cell adhesion, growth and differentiation. Bone formation was assessed by immunohistochemical staining, micro-CT and hematoxylin and eosin staining. Results: The isolated hUC-MSCs expressed CD105, CD90 and CD73, did not express CD45, CD34, CD11a and HLA-DR, exhibited self-renewal potential, and favored osteogenesis and adipogenesis. The exogenously-added rhBMP-7 attenuated the inhibitory effect of the serum-free osteogenic media (OMD) on the proliferation of hUC-MSCs combined with nHAC/PLA, increased the promoting effect of OMD on osteogenic differentiation of hUC-MSCs in two or three-dimensional culture, and enhanced its heterotopic bone formation and jaw bone defect repair abilities. Furthermore, the bone formation of in situ bone defect was significantly superior to heterotopic bone formation. Conclusions: That the microenvironment formed by the regenerative engineered constructs and the in situ bone defect microenvironment closely matched that of the bone tissue in its native state may be essential for sufficient and timely bone regeneration. The endogenously-produced BMPs may serve an important regulatory role in the process. These results paved the way for developing allogeneic hUC-MSCs-based constructs for clinical jaw bone regenerative therapeutic applications.

scholarly journals Bone morphogenetic protein-induced heterotopic bone formation: What have we learned from the history of a half century?

2015 ◽  
Vol 51 (2) ◽  
pp. 42-50 ◽  
Author(s):  
Takenobu Katagiri ◽  
Kenji Osawa ◽  
Sho Tsukamoto ◽  
Mai Fujimoto ◽  
Arei Miyamoto ◽  
...  
Keyword(s):  
Bone Formation ◽  
Bone Morphogenetic Protein ◽  
Heterotopic Bone ◽  
Heterotopic Bone Formation ◽  
Half Century ◽  
Morphogenetic Protein ◽  
History Of

Complications associated with recombinant human bone morphogenetic protein use in pediatric craniocervical arthrodesis

2011 ◽  
Vol 7 (5) ◽  
pp. 468-474 ◽  
Author(s):  
Timothy E. Lindley ◽  
Nader S. Dahdaleh ◽  
Arnold H. Menezes ◽  
Kingsley O. Abode-Iyamah
Keyword(s):  
Bone Morphogenetic Protein ◽  
Case Series ◽  
Fusion Rate ◽  
Human Bone ◽  
Heterotopic Bone ◽  
Heterotopic Bone Formation ◽  
Occipitocervical Fusion ◽  
Morphogenetic Protein ◽  
Human Bone Morphogenetic Protein ◽  
Recombinant Human Bone

Object Management of pediatric occipitocervical instability remains especially challenging. The off-label use of recombinant human bone morphogenetic protein (rhBMP)-2 for spinal fusion has increased with a well-documented increase in fusion rate in many case series. Unfortunately, recent reports have documented complications associated with rhBMP use in adult spinal fusions. Complications associated with the use of rhBMP in pediatric spinal surgery is less well understood. In this study the authors report on the fusion rate and complications associated with rhBMP in pediatric occipitocervical arthrodesis. Methods The authors reviewed the medical records of those patients 18 years old and younger who underwent dorsal occipitocervical fusion from January 2004 to December 2007 at the University of Iowa Hospitals and Clinics. Forty-eight patients were identified who received rhBMP-augmented fusion. The clinical outcome and complications of these fusions were analyzed. Results All 48 patients had fusion confirmed on lateral radiographs within 4–14 months with an average fusion time of 6.7 months. There were 6 complications, 5 of which included seroma formation. Two of 5 patients who developed postoperative seroma presented with symptoms suggesting brainstem compression and obstructive hydrocephalus requiring emergency reoperation. One patient developed heterotopic bone formation causing cervicomedullary compression requiring reoperation. Conclusions The use of rhBMP to augment autograft in occipitocervical fusion allows for a high rate of successful arthrodesis, but is associated with potentially life-threatening complications in pediatric patients.

scholarly journals Imaging symptomatic bone morphogenetic protein-2–induced heterotopic bone formation within the spinal canal: case report

2016 ◽  
Vol 24 (5) ◽  
pp. 857-861 ◽  
Author(s):  
Timothy Chryssikos ◽  
Kenneth M. Crandall ◽  
Charles A. Sansur
Keyword(s):  
Bone Formation ◽  
Bone Morphogenetic Protein ◽  
Spinal Canal ◽  
Imaging Techniques ◽  
Cauda Equina ◽  
Plain Film ◽  
Bone Morphogenetic Protein 2 ◽  
Heterotopic Bone ◽  
Heterotopic Bone Formation ◽  
Morphogenetic Protein

Heterotopic bone formation within the spinal canal is a known complication of bone morphogenetic protein–2 (BMP-2) and presents a clinical and surgical challenge. Imaging modalities are routinely used for operative planning in this setting. Here, the authors present the case of a 59-year-old woman with cauda equina syndrome following intraoperative BMP-2 administration. Plain film myelographic studies showed a region of severe stenosis that was underappreciated on CT myelography due to a heterotopic bony lesion mimicking the dorsal aspect of a circumferentially patent thecal sac. When evaluating spinal stenosis under these circumstances, it is important to carefully consider plain myelographic images in addition to postmyelography CT images as the latter may underestimate the true degree of stenosis due to the potentially similar radiographic appearances of evolving BMP-2–induced heterotopic bone and intrathecal contrast. Alternatively, comparison of sequentially acquired noncontrast CT scans with CT myelographic images may also assist in distinguishing BMP-2–induced heterotopic bony lesions from the thecal sac. Further studies are needed to elucidate the roles of the available imaging techniques in this setting and to characterize the connection between the radiographic and histological appearances of BMP-2–induced heterotopic bone.

Evaluation of Heterotopic Bone Formation Induced by Squalane and Bone Morphogenetic Protein Composite

1997 ◽  
Vol 337 ◽  
pp. 261-266 ◽  
Author(s):  
Toshiyuki Kawakami ◽  
Tatsushi Kawai ◽  
Noriyuki Takei ◽  
Toshihiko Kise ◽  
Shigeo Eda ◽  
...  
Keyword(s):  
Bone Formation ◽  
Bone Morphogenetic Protein ◽  
Heterotopic Bone ◽  
Heterotopic Bone Formation ◽  
Morphogenetic Protein

scholarly journals Overexpression of bone morphogenetic protein 2 through aberrant canonical Wnt/β-catenin signaling pathway plays an important role in heterotopic ossification of adrenal myelolipoma

2014 ◽  
Vol 8 (1-2) ◽  
pp. 104 ◽  
Author(s):  
Yozo Mitsui ◽  
Hiroaki Yasumoto ◽  
Miho Hiraki ◽  
Naoko Arichi ◽  
Noriyoshi Ishikawa ◽  
...  
Keyword(s):  
Bone Formation ◽  
Heterotopic Ossification ◽  
Bone Morphogenetic Protein ◽  
Signaling Pathway ◽  
Bone Morphogenetic Protein 2 ◽  
Heterotopic Bone ◽  
Heterotopic Bone Formation ◽  
Adrenal Myelolipoma ◽  
Morphogenetic Protein ◽  
Canonical Wnt

The precise mechanism of heterotopic ossification caused by several types of tumours is largely unknown. However, recent studies have indicated that bone morphogenetic protein 2 (BMP2) is closely linked to the Wnt/β-catenin signaling pathway in this rare phenomenon of bone formation. We report a rare case of adrenal myelolipoma (ML) in a 27-year-old woman with heterotopic bone formation. Immunohistochemical findings showed BMP2 expression in the cytoplasm of tumour cells, as well as the matrix adjacent to newly developed bone tissue. In addition, β-catenin was prominent in the cytoplasm and nuclei of BMP2-positive tumour cells. To the best of our knowledge, this is the first report of adrenal ML showing heterotopic ossification with accelerated expression of both BMP2 and β-catenin. Our case findings indicate that BMP2 overexpression via aberrant canonical Wnt/β-catenin signaling may contribute to heterotopic bone formation occurring in adrenal ML.

Sign in / Sign up

Export Citation Format

Share Document