Heterotopic Ossification: Two Rare Forms and What They Can Teach Us

Kaplan, Frederick S.; Hahn, Gregory V.; Zasloff, Michael

doi:10.5435/00124635-199409000-00007

Cited by 85 publications

(54 citation statements)

References 24 publications

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“…The first is characterized by ectopic bone formation within the subcutaneous adipose layer of the skin [4,[6][7][8]. Closer observations to these ectopic formations also revealed the presence of osteoblasts and chondrocytes, in addition to adipocytes [6], which were a clear indication of the presence of a multipotent stem cell population within the adipose tissue. In addition to this, obesity further reinforced this hypothesis [4,5].…”

Section: Synopsis Of Ascs Basic Biologymentioning

confidence: 95%

Adipose Tissue Derived Stem Cells Secretome: Soluble Factors and Their Roles in Regenerative Medicine

Salgado

Reis²,

Sousa³

et al. 2010

CSCR

529

217

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Stem cells have been long looked at as possible therapeutic vehicles for different health related problems. Among the different existing stem cell populations, Adipose derived Stem Cells (ASCs) have been gathering attention in the last 10 years. When compared to other stem cells populations and sources, ASCs can be easily isolated while providing higher yields upon the processing of adipose tissue. Similar to other stem cell populations, it was initially thought that the main potential of ASCs for regenerative medicine approaches was intimately related to their differentiation capability. Although this is true, there has been an increasing body of literature describing the trophic effects of ASCs on the protection, survival and differentiation of a variety of endogenous cells/tissues. Moreover, they have also shown to possess an immunomodulatory character. This effect is closely related to the ASCs' secretome and the soluble factors found within it. Molecules such as hepatocyte growth factor (HGF), granulocyte and macrophage colony stimulating factors, interleukins (ILs) 6, 7, 8 and 11, tumor necrosis factor-(TNF-), vascular endothelial growth factor (VEGF), brain derived neurotrophic factor (BDNF), nerve growth factor (NGF), adipokines and others have been identified within the ASCs' secretome. Due to its importance regarding future applications for the field of regenerative medicine, we aim, in the present review, to make a comprehensive analysis of the literature relating to the ASCs' secretome and its relevance to the immune and central nervous system, vascularization and cardiac regeneration. The concluding section will highlight some of the major challenges that remain before ASCs can be used for future clinical applications.

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Section: Synopsis Of Ascs Basic Biologymentioning

confidence: 95%

Adipose Tissue Derived Stem Cells Secretome: Soluble Factors and Their Roles in Regenerative Medicine

Salgado

Reis²,

Sousa³

et al. 2010

CSCR

529

217

View full text Add to dashboard Cite

show abstract

“…Its development is thought to stem from an alteration in normal skeletogenesis [4,11] and can occur in the context of musculoskeletal trauma, spinal cord injury, burns, or traumatic brain injury [1-3, 6, 9].…”

Section: Introductionmentioning

confidence: 99%

Risk Factors for the Development of Heterotopic Ossification After Knee Dislocation

Whelan

Dold

Trajkovski

et al. 2014

Clinical Orthopaedics &Amp; Related Research

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Background Results of treatment for acute knee dislocations and multiligament knee injuries may be influenced by a multitude of patient-and injury-related factors, including neurologic function, vascular status, ipsilateral fractures, and joint stability. The development of heterotopic ossification (HO) may nullify any benefits of reconstruction, because it can cause stiffness and discomfort. Identifying factors associated with HO after knee dislocation may help identify patients who might benefit from prophylaxis. Questions/purposes The purposes of this study were (1) to identify specific risk factors for the development of HO in patients with knee dislocation; and (2) to elucidate the relationship between the presence of absence of HO and postoperative range of motion. Methods Between 2005 and 2010, we performed 101 multiligament reconstructions for patients with knee dislocations, of which 91 (90%) in 91 patients were available for followup at a minimum of 6 months (mean, 18 months; range, 6-44 months), and were reviewed here. AP and lateral radiographs were reviewed for all patients and HO was classified according to the Mills and Tejwani classification system. This knee dislocation cohort was separated into two groups based on the presence or absence of HO for comparison. Using a significance level of p \ 0.05 for factors in the univariate analyses, we identified potential variables for a multivariate logistic regression model to identify risk factors predicting development of HO in patients with multiligament knee injuries; multivariate analysis then was performed to mitigate the influence of potentially confounding variables. Thirty patients (34%) developed HO after multiligament knee injury in our series. Results Posterior cruciate ligament reconstruction was the only independent predictor of HO that we identified (odds ratio, 6.3; 95% confidence interval, 1.2-34.6). Patients who developed HO were more likely to develop stiff knees and undergo surgery (50%; 15 of 30 patients) versus those without HO (12%; seven of 58 patients) to attempt to restore functional range of motion (p \ 0.001). Conclusions HO is a common complication after knee dislocation and can diminish range of motion and cause patients to undergo further surgery. Posterior cruciate ligament reconstruction is an independent risk factor for the development of HO. Strategies to identify risk factors for, and safe prevention of, HO after multiple ligament injury and surgery should be investigated going forward.

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“…BMP-2 and BMP-4 have been suggested to exclusively induce endochondral ossification [22,25], whereas other investigators have reported simultaneous endochondral and intramembranous bone formation induced by BMP-2 [20,42]. Similarly, the study of rare human genetic diseases [12,17,18,40], such as fibrodysplasia ossificans progressiva and progressive osseous heteroplasia, has provided insight into this condition. Yet, extrapolation of the findings from these studies may have only limited applicability to HO as seen after THA.…”

Section: Introductionmentioning

confidence: 99%

“…Yet, extrapolation of the findings from these studies may have only limited applicability to HO as seen after THA. For example, fibrodysplasia ossificans progressiva exhibits characteristics of endochondral ossification whereas progressive osseous heteroplasia is largely characterized by intramembranous ossification [12,[17][18][19]. Consequently, elucidation of the predominant pathway of HO as observed after surgical trauma in humans is critically dependent on identification of an appropriate animal model in which to study the process.…”

Section: Introductionmentioning

confidence: 99%

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Heterotopic Bone Formation About the Hip Undergoes Endochondral Ossification: A Rabbit Model

Tannous¹,

Stall²,

Griffith³

et al. 2013

Clinical Orthopaedics &Amp; Related Research

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Background Heterotopic ossification (HO) occurs most commonly after trauma and surgery about the hip and may compromise subsequent function. Currently available animal models describing the cellular progression of HO are based on exogenous osteogenic induction agents and may not reflect the processes following trauma.Questions/purposes We therefore sought to characterize the histologic progression of heterotopic bone formation in an animal model that recapitulates the human condition without the addition of exogenous osteogenic material. Methods We used a rabbit model that included intramedullary instrumentation of the upper femur and ischemic crush injury of the gluteal muscle. Bilateral surgical induction procedures were performed on 30 animals with the intention of inciting the process of HO; no supplemental osteogenic stimulants were used. Three animals were sacrificed at each of 10 predetermined times between 1 day and 26 weeks postoperatively and the progression of tissue maturation was graded histologically using a five-item scale. Results Heterotopic bone reliably formed de novo and consistently followed a pathway of endochondral ossification. Chondroid elements were found in juxtaposition with immature woven bone in all sections that contained mature osseous elements. Conclusions These results establish that HO occurs in an animal model mimicking the human condition following surgical trauma about the hip; it is predictable in its histologic progression and follows a pathway of endochondral bone formation. Clinical Relevance By showing a consistent pathway of endochondral ossification leading to ectopic bone formation, this study provides a basis for understanding the mechanisms by which HO might be mitigated by interventions.

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Heterotopic Ossification: Two Rare Forms and What They Can Teach Us

Cited by 85 publications

References 24 publications

Adipose Tissue Derived Stem Cells Secretome: Soluble Factors and Their Roles in Regenerative Medicine

Adipose Tissue Derived Stem Cells Secretome: Soluble Factors and Their Roles in Regenerative Medicine

Risk Factors for the Development of Heterotopic Ossification After Knee Dislocation

Heterotopic Bone Formation About the Hip Undergoes Endochondral Ossification: A Rabbit Model

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