A comparison of tissue engineering based repair of calvarial defects using adipose stem cells from normal and osteoporotic rats

Pei, Ming; Li, Jingting; McConda, David B.; Wen, Sijin; Clovis, Nina; Danley, Suzanne S.

doi:10.1016/j.bone.2015.04.040

Cited by 22 publications

(18 citation statements)

References 42 publications

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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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“…In recent years, stem cell transplantation has been an alternative option for the treatment of bone nonunion [3,29,30]. MSCs are considered one of the most suitable types of stem cells for autologous transplantation therapy because of their bone regeneration potential [31,32]. BMMSC transplantation has been proven effective in enhancing osteogenesis and angiogenesis [33].…”

Section: Discussionmentioning

confidence: 99%

Exosomes from bone marrow mesenchymal stem cells enhance fracture healing through the promotion of osteogenesis and angiogenesis in a rat model of nonunion

et al. 2020

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Background: As important players in cell-to-cell communication, exosomes (exo) are believed to play a similar role in promoting fracture healing. This study investigated whether exosomes derived from bone marrow mesenchymal stem cells (BMMSC-Exos) could improve fracture healing of nonunion. Methods: BMMSC-Exos were isolated and transplanted into the fracture site in a rat model of femoral nonunion (Exo group) every week. Moreover, equal volumes of phosphate-buffered saline (PBS) and exosome-depleted conditioned medium (CM-Exo) were injected into the femoral fracture sites of the rats in the control and CM-Exo groups. Bone healing processes were recorded and evaluated by radiographic methods on weeks 8, 14 and 20 after surgery. Osteogenesis and angiogenesis at the fracture sites were evaluated by radiographic and histological methods on postoperative week 20. The expression levels of osteogenesis-or angiogenesis-related genes were evaluated in vitro by western blotting and immunohistochemistry. The ability to internalize exosomes was assessed using the PKH26 assay. Altered proliferation and migration of human umbilical vein endothelial cells (HUVECs) and mouse embryo osteoblast precursor cells (MC3TE-E1s) treated with BMMSC-Exos were determined by utilizing EdU incorporation, immunofluorescence staining, and scratch wound assay. The angiogenesis ability of HUVECs was evaluated through tube formation assays. Finally, to explore the effect of exosomes in osteogenesis via the BMP-2/ Smad1/RUNX2 signalling pathway, the BMP-2 inhibitors noggin and LDN193189 were utilized, and their subsequent effects were observed. Results: BMMSC-Exos were observed to be spherical with a diameter of approximately 122 nm. CD9, CD63 and CD81 were expressed. Transplantation of BMMSC-Exos obviously enhanced osteogenesis, angiogenesis and bone healing processes in a rat model of femoral nonunion. BMMSC-Exos were taken up by HUVECs and MC3T3-E1 in vitro, and their proliferation and migration were also improved. Finally, experiments with BMP2 inhibitors confirmed that the BMP-2/Smad1/RUNX2 signalling pathway played an important role in the pro-osteogenesis induced by BMMSC-Exos and enhanced fracture healing of nonunion.

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“…Similarly, ASCs from ovariectomized rats exhibited a comparable proliferation capacity compared with controls, but showed relatively lower osteogenic potential in a critical-size calvarial defect model [188].…”

Section: Ascs-based Bone Regeneration In Geriatric Applicationsmentioning

confidence: 93%

Adipose-derived stem cell therapies for bone regeneration

Barba

Taranto

Lattanzi

2017

Expert Opinion on Biological Therapy

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Cell-based therapies exploit the heterogeneous and self-sufficient biological environment of stem cells to restore, maintain and improve tissue functions. Adipose-derived stem cells (ASCs) are, to this aim, promising cell types thanks to advantageous isolation procedures, growth kinetics, plasticity and trophic properties. Specifically, bone regeneration represents a suitable, though often challenging, target setting to test and apply ASC-based therapeutic strategies. Areas covered: ASCs are extremely plastic and secrete bioactive peptides that mediate paracrine functions, mediating their trophic actions in vivo. Numerous preclinical studies demonstrated that ASCs improve bone healing. Clinical trials are ongoing to validate the clinical feasibility of these approaches. This review is intended to define the state-of-the-art on ASCs, encompassing the biological features that make them suitable for bone regenerative strategies, and to provide an update on existing preclinical and clinical applications. Expert opinion: ASCs offer numerous advantages over other stem cells in terms of feasibility of clinical translation. Data obtained from in vivo experimentation are encouraging, and clinical trials are ongoing. More robust validations are thus expected to be achieved during the next few years, and will likely pave the way to optimized patient-tailored treatments for bone regeneration.

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A comparison of tissue engineering based repair of calvarial defects using adipose stem cells from normal and osteoporotic rats

Cited by 22 publications

References 42 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

Exosomes from bone marrow mesenchymal stem cells enhance fracture healing through the promotion of osteogenesis and angiogenesis in a rat model of nonunion

Adipose-derived stem cell therapies for bone regeneration

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