The effects of local insulin application to lumbar spinal fusions in a rat model

Koerner, John D.; Yalamanchili, Praveen; Munoz, William; Uko, Linda; Chaudhary, Saad B.; Lin, Sheldon S.; Vives, Michael J.

doi:10.1016/j.spinee.2012.11.030

Cited by 25 publications

(22 citation statements)

References 30 publications

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“…As previously discussed, autogenous bone grafting, the gold standard of care for spinal fusion procedures, is limited in its use because of limited donor availability, additional surgical trauma and donor site morbidity [8–10]. Moreover, previously published rat spinal fusion studies assessing autologous bone grafting were observed to yield an inferior fusion rate when compared with hPSC treatment (0% fusion after 4 weeks and 11% fusion after 8 weeks with autologous bone grafting, compared with 80%–100% fusion in 4 weeks with hPSC treatment) [46, 47]. MSCs derived from multiple sources such as bone marrow and adipose tissue have attracted large interest for replacement of autogenous bone in spinal fusion procedures [48–52].…”

Section: Discussionmentioning

confidence: 99%

Human Perivascular Stem Cell-Based Bone Graft Substitute Induces Rat Spinal Fusion

Chung

James

Asatrian

et al. 2014

Stem Cells Translational Medicine

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Adipose tissue is an attractive source of mesenchymal stem cells (MSCs) because of its abundance and accessibility. We have previously defined a population of native MSCs termed perivascular stem cells (PSCs), purified from diverse human tissues, including adipose tissue. Human PSCs (hPSCs) are a bipartite cell population composed of pericytes (CD146+CD34-CD45-) and adventitial cells (CD146-CD34+CD45-), isolated by fluorescence-activated cell sorting and with properties identical to those of culture identified MSCs. Our previous studies showed that hPSCs exhibit improved bone formation compared with a sample-matched unpurified population (termed stromal vascular fraction); however, it is not known whether hPSCs would be efficacious in a spinal fusion model. To investigate, we evaluated the osteogenic potential of freshly sorted hPSCs without culture expansion and differentiation in a rat model of posterolateral lumbar spinal fusion. We compared increasing dosages of implanted hPSCs to assess for dose-dependent efficacy. All hPSC treatment groups induced successful spinal fusion, assessed by manual palpation and microcomputed tomography. Computerized biomechanical simulation (finite element analysis) further demonstrated bone fusion with hPSC treatment. Histological analyses showed robust endochondral ossification in hPSC-treated samples. Finally, we confirmed that implanted hPSCs indeed differentiated into osteoblasts and osteocytes; however, the majority of the new bone formation was of host origin. These results suggest that implanted hPSCs positively regulate bone formation via direct and paracrine mechanisms. In summary, hPSCs are a readily available MSC population that effectively forms bone without requirements for culture or predifferentiation. Thus, hPSC-based products show promise for future efforts in clinical bone regeneration and repair.

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Section: Discussionmentioning

confidence: 99%

Human Perivascular Stem Cell-Based Bone Graft Substitute Induces Rat Spinal Fusion

Chung

James

Asatrian

et al. 2014

Stem Cells Translational Medicine

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“…Diabetes delays the postoperative bone healing process stimulated by enhanced tumor necrosis factor α to reduce proliferation and promote necrosis of mesenchymal stem cells 17) . Additionally, local insulin concentration can affect the fusion results by modifying the level of insulin like growth factor-1 at the fusion site 18) . Smoking also affects bone formation.…”

Section: Discussionmentioning

confidence: 99%

Matched Comparison of Fusion Rates between Hydroxyapatite Demineralized Bone Matrix and Autograft in Lumbar Interbody Fusion

Kim

Lee

Shin

et al. 2016

J Korean Neurosurg Soc

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ObjectiveTo compare the fusion rate of a hydroxyapatite demineralized bone matrix (DBM) with post-laminectomy acquired autograft in lumbar interbody fusion surgery and to evaluate the correlation between fusion rate and clinical outcome.MethodsFrom January 2013 to April 2014, 98 patients underwent lumbar interbody fusion surgery with hydroxyapatite DBM (HA-DBM group) in our institute. Of those patients, 65 received complete CT scans for 12 months postoperatively in order to evaluate fusion status. For comparison with autograft, we selected another 65 patients who underwent lumbar interbody fusion surgery with post-laminectomy acquired autograft (Autograft group) during the same period. Both fusion material groups were matched in terms of age, sex, body mass index (BMI), and bone mineral density (BMD). To evaluate the clinical outcomes, we analyzed the results of visual analogue scale (VAS), Oswestry Disability Index (ODI), and Short Form Health Survey (SF-36).ResultsWe reviewed the CT scans of 149 fusion levels in 130 patients (HA-DBM group, 75 levels/65 patients; Autograft group, 74 levels/65 patients). Age, sex, BMI, and BMD were not significantly different between the groups (p=0.528, p=0.848, p=0.527, and p=0.610, respectively). The HA-DBM group showed 39 of 75 fused levels (52%), and the Autograft group showed 46 of 74 fused levels (62.2%). This difference was not statistically significant (p=0.21). In the HA-DBM group, older age and low BMD were significantly associated with non-fusion (61.24 vs. 66.68, p=0.027; -1.63 vs. -2.29, p=0.015, respectively). VAS and ODI showed significant improvement after surgery when fusion was successfully achieved in both groups (p=0.004, p=0.002, HA-DBM group; p=0.012, p=0.03, Autograft group).ConclusionThe fusion rates of the hydroxyapatite DBM and Autograft groups were not significantly different. In addition, clinical outcomes were similar between the groups. However, older age and low BMD are risk factors that might induce non-union after surgery with hydroxyapatite DBM.

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“…As previously discussed, autogenous bone grafting, the gold standard of care for spinal fusion procedures, is limited in its use because of limited donor availability, additional surgical trauma and donor site morbidity [8][9][10]. Moreover, previously published rat spinal fusion studies assessing autologous bone grafting were observed to yield an inferior fusion rate when compared with hPSC treatment (0% fusion after 4 weeks and 11% fusion after 8 weeks with autologous bone grafting, compared with 80%-100% fusion in 4 weeks with hPSC treatment) [46,47]. MSCs derived from multiple sources such as bone marrow and adipose tissue have attracted large interest for replacement of autogenous bone in spinal fusion procedures [48][49][50][51][52].…”

Section: Discussionmentioning

confidence: 99%

Human Perivascular Stem Cell-Based Bone Graft Substitute Induces Rat Spinal Fusion

Chung

James

Asatrian

et al. 2015

Stem Cells Translational Medicine

View full text Add to dashboard Cite

Adipose tissue is an attractive source of mesenchymal stem cells (MSCs) because of its abundance and accessibility. We have previously defined a population of native MSCs termed perivascular stem cells (PSCs), purified from diverse human tissues, including adipose tissue. Human PSCs (hPSCs) are a bipartite cell population composed of pericytes (CD146+CD342CD452) and adventitial cells (CD1462CD34+ CD452), isolated by fluorescence-activated cell sorting and with properties identical to those of culture identified MSCs. Our previous studies showed that hPSCs exhibit improved bone formation compared with a sample-matched unpurified population (termed stromal vascular fraction); however, it is not known whether hPSCs would be efficacious in a spinal fusion model. To investigate, we evaluated the osteogenic potential of freshly sorted hPSCs without culture expansion and differentiation in a rat model of posterolateral lumbar spinal fusion. We compared increasing dosages of implanted hPSCs to assess for dose-dependent efficacy. All hPSC treatment groups induced successful spinal fusion, assessed by manual palpation and microcomputed tomography. Computerized biomechanical simulation (finite element analysis) further demonstrated bone fusion with hPSC treatment. Histological analyses showed robust endochondral ossification in hPSC-treated samples. Finally, we confirmed that implanted hPSCs indeed differentiated into osteoblasts and osteocytes; however, the majority of the new bone formation was of host origin. These results suggest that implanted hPSCs positively regulate bone formation via direct and paracrine mechanisms. In summary, hPSCs are a readily available MSC population that effectively forms bone without requirements for culture or predifferentiation. Thus, hPSC-based products show promise for future efforts in clinical bone regeneration and repair. STEM CELLS

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The effects of local insulin application to lumbar spinal fusions in a rat model

Cited by 25 publications

References 30 publications

Human Perivascular Stem Cell-Based Bone Graft Substitute Induces Rat Spinal Fusion

Human Perivascular Stem Cell-Based Bone Graft Substitute Induces Rat Spinal Fusion

Matched Comparison of Fusion Rates between Hydroxyapatite Demineralized Bone Matrix and Autograft in Lumbar Interbody Fusion

Human Perivascular Stem Cell-Based Bone Graft Substitute Induces Rat Spinal Fusion

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