Human Adipose Derived Stromal Cells Heal Critical Size Mouse Calvarial Defects

Lévi, Benjamin; James, Aaron W.; Nelson, Emily R.; Vistnes, Dean; Wu, Benjamin M.; Lee, Min; Gupta, Ankur; Longaker, Michael T.

doi:10.1371/journal.pone.0011177

Cited by 258 publications

(323 citation statements)

References 46 publications

(61 reference statements)

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“…We decided to use ASCs mainly because of their great accessibility and low patient morbidity when compared with other mesenchymal cell sources such as bone marrow or periosteum. The in vitro, in vivo and clinical bone‐forming capacity of ASCs in combination with various scaffold materials have been reported by many authors 14, 20, 35, 36, 37, 38, 39, 40, 41. In this series, the flow cytometric characterization of the ASCs expanded in autologous serum corresponded to previously published results for ASCs 42, 43.…”

Section: Discussionsupporting

confidence: 86%

Cranioplasty with Adipose-Derived Stem Cells, Beta-Tricalcium Phosphate Granules and Supporting Mesh: Six-Year Clinical Follow-Up Results

Thesleff

Lehtimäki

Niskakangas

et al. 2017

Stem Cells Translational Medicine

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Several alternative techniques exist to reconstruct skull defects. The complication rate of the cranioplasty procedure is high and the search for optimal materials and techniques continues. To report long‐term results of patients who have received a cranioplasty using autologous adipose‐derived stem cells (ASCs) seeded on beta‐tricalcium phosphate (betaTCP) granules. Between 10/2008 and 3/2010, five cranioplasties were performed (four females, one male; average age 62.0 years) using ASCs, betaTCP granules and titanium or resorbable meshes. The average defect size was 8.1 × 6.7 cm2. Patients were followed both clinically and radiologically. The initial results were promising, with no serious complications. Nevertheless, in the long‐term follow‐up, three of the five patients were re‐operated due to graft related problems. Two patients showed marked resorption of the graft, which led to revision surgery. One patient developed a late infection (7.3 years post‐operative) that required revision surgery and removal of the graft. One patient had a successfully ossified graft, but was re‐operated due to recurrence of the meningioma 2.2 years post‐operatively. One patient had an uneventful clinical follow‐up, and the cosmetic result is satisfactory, even though skull x‐rays show hypodensity in the borders of the graft. Albeit no serious adverse events occurred, the 6‐year follow‐up results of the five cases are unsatisfactory. The clinical results are not superior to results achieved by conventional cranial repair methods. The use of stem cells in combination with betaTCP granules and supporting meshes in cranial defect reconstruction need to be studied further before continuing with clinical trials. Stem Cells Translational Medicine 2017;6:1576–1582

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Section: Discussionsupporting

confidence: 86%

Cranioplasty with Adipose-Derived Stem Cells, Beta-Tricalcium Phosphate Granules and Supporting Mesh: Six-Year Clinical Follow-Up Results

Thesleff

Lehtimäki

Niskakangas

et al. 2017

Stem Cells Translational Medicine

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“…The critical-sized calvarial defect model has been validated as model to study skeletal regeneration using both murine adipose-derived stromal cells 6 and human-derived adipose-derived stromal cells 1 . The creation of a 4 mm defect in the right parietal calvaria of a mouse will not heal in the lifetime of the animal.…”

Section: Discussionmentioning

confidence: 99%

Repair of a Critical-sized Calvarial Defect Model Using Adipose-derived Stromal Cells Harvested from Lipoaspirate

Hyun

Chung

et al. 2012

JoVE

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Craniofacial skeletal repair and regeneration offers the promise of de novo tissue formation through a cell-based approach utilizing stem cells. Adipose-derived stromal cells (ASCs) have proven to be an abundant source of multipotent stem cells capable of undergoing osteogenic, chondrogenic, adipogenic, and myogenic differentiation. Many studies have explored the osteogenic potential of these cells in vivo with the use of various scaffolding biomaterials for cellular delivery. It has been demonstrated that by utilizing an osteoconductive, hydroxyapatitecoated poly(lactic-co-glycolic acid) (HA-PLGA) scaffold seeded with ASCs, a critical-sized calvarial defect, a defect that is defined by its inability to undergo spontaneous healing over the lifetime of the animal, can be effectively show robust osseous regeneration. This in vivo model demonstrates the basis of translational approaches aimed to regenerate the bone tissue -the cellular component and biological matrix. This method serves as a model for the ultimate clinical application of a progenitor cell towards the repair of a specific tissue defect. Video LinkThe video component of this article can be found at

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“…Although ADSCs can survive a long period and undergo osteogenic differentiation in vivo [10], they may also contribute through paracrine pathways. The adiposederived cells secrete angiogenic cytokines such as BMP-2, VEGF, SDF-1, and IL-6, which are postulated to contribute to the osteogenic and angiogenic properties of ASDCs [14,16].…”

Section: Discussionmentioning

confidence: 99%

Uncultured Autogenous Adipose-derived Regenerative Cells Promote Bone Formation During Distraction Osteogenesis in Rats

Nomura

Watanabe

Matsubara

et al. 2014

Clin Orthop Relat Res

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Background Adipose-derived stem cells have recently shown differentiation potential in multiple mesenchymal lineages in vitro and in vivo. These cells can be easily isolated in large amounts from autologous adipose tissue and used without culturing or differentiation induction, which may make them relatively easy to use for clinical purposes; however, their use has not been tested in a distraction osteogenesis model. Question/purposes The question of this animal study in a rodent model of distraction osteogenesis was whether uncultured adipose-derived regenerative cells (ADRCs), which can easily be isolated in large amounts from autologous adipose tissue and contain several types of stem and regenerative cells, promote bone formation in distraction osteogenesis. We evaluated this using several tools: (1) radiographic analysis of bone density; (2) histological analysis of the callus that formed; (3) biomechanical testing; (4) DiI labeling (a method of membrane staining for postimplant celltracing); and (5) real-time polymerase chain reaction. Methods Sixty rats were randomly assigned to three groups. Physiological saline (control group), Type I collagen gel (collagen group), or a mixture of ADRC and Type I collagen gel (ADRC group) was injected into the distracted callus immediately after distraction termination. To a rat femur an external fixator was applied at a rate of 0.8 mm/day for 8 days.Results The bone density of the distracted callus in the ADRC group increased by 46% (p = 0.003, Cohen's d = 10.2, 95% confidence interval [CI] ± 0.180) compared with the control group at 6 weeks after injection. The fracture strength in the ADRC group increased by 66% (p = 0.006, Cohen's d = 1.32, 95% CI ± 0.180) compared with the control group at 6 weeks after injection. Real-time reverse transcription-polymerase chain reaction of the distracted callus from the ADRC group had higher levels of bone morphogenetic protein-2 (7.4 times higher), vascular endothelial growth factor A (6.8 times higher), and stromal cell-derived factor-1 (4.3 times higher). Cell labeling in the newly formed bone showed the ADRCs differentiated into osseous tissue at 3 weeks after injection. Conclusions The injection of ADRCs promoted bone formation in the distracted callus and this mechanism involves both osteogenic differentiation and secretion of humoral factors such as bone morphogenetic protein-2 or vascular endothelial growth factor A that promotes osteogenesis or angiogenesis.

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Human Adipose Derived Stromal Cells Heal Critical Size Mouse Calvarial Defects

Cited by 258 publications

References 46 publications

Cranioplasty with Adipose-Derived Stem Cells, Beta-Tricalcium Phosphate Granules and Supporting Mesh: Six-Year Clinical Follow-Up Results

Cranioplasty with Adipose-Derived Stem Cells, Beta-Tricalcium Phosphate Granules and Supporting Mesh: Six-Year Clinical Follow-Up Results

Repair of a Critical-sized Calvarial Defect Model Using Adipose-derived Stromal Cells Harvested from Lipoaspirate

Uncultured Autogenous Adipose-derived Regenerative Cells Promote Bone Formation During Distraction Osteogenesis in Rats

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