Comparison of Human Mesenchymal Stem Cells Derived From Adipose Tissue and Bone Marrow for Ex Vivo Gene Therapy in Rat Spinal Fusion Model

Miyazaki, Masashi; Zuk, Patricia A.; Zou, Jun; Yoon, Seung Hwan; Wei, Feng; Morishita, Yuichiro; Sintuu, Chananit; Wang, Jeffrey C.

doi:10.1097/brs.0b013e31816b45c3

Cited by 92 publications

(72 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…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]. BMSCs, however, are limited in supply, and it is estimated that only 1 BMSC can be isolated per 100,000 cells [53].…”

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

show abstract

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

show abstract

“…[32][33][34][35] Radiographic analysis (Fig. 3) revealed that the new bone mass between the L4 and L5 transverse processes in the Nell-1 (5.0 mg) group was the most radiopaque, and a continuous bony bridge formed between the transverse processes.…”

Section: Radiography and Manual Palpationmentioning

confidence: 99%

“…Bone formation in these groups was compared to our previously established positive control of absorbable collagen sponges impregnated with 10 mg recombinant human BMP-2. [32][33][34][35] After anesthesia induction by isoflurane inhalation, the surgical site was shaved and prepped. A posterior midline incision was made over the skin of the lumbar spine.…”

Section: Surgical Procedures and Study Groupsmentioning

confidence: 99%

Delivery of Lyophilized Nell-1 in a Rat Spinal Fusion Model

Lee

Whang

et al. 2010

Tissue Engineering Part A

Self Cite

View full text Add to dashboard Cite

Nell-1 (Nel-like molecule-1; Nel: protein strongly expressed in neural tissue containing epidermal growth factorlike domain) is a promising osteoblast-specific growth factor for osteoinductive therapies that may circumvent adverse effects, such as nonspecific function and ectopic bone formation, associated with more established osteogenic growth factors such as bone morphogenetic proteins. Beta-tricalcium phosphate (b-TCP), an osteoconductive, biodegradable ceramic biomaterial, has been used successfully to deliver osteoinducers for bone regeneration. The aim of this study was to develop a carrier system for efficiently delivering biologically active Nell-1 protein. After a 40% initial burst release, b-TCP particles retained the majority of adsorbed Nell-1 protein in vitro. To test this system in vivo, L4/L5 spinal fusion was performed in three groups of rats (n ¼ 8 each): (1) 5 mg Nell-1 in b-TCP/demineralized bone matrix putty (DBX); (2) 2.5 mg Nell-1 in b-TCP/DBX; (3) b-TCP/DBX only. Fusion was assessed by radiography, palpation, microcomputed tomography, and histological analysis. After 4 weeks, 75% of Nell-1-treated animals exhibited fusion, with a significant increase in new bone volume, whereas only 25% of Nell-free control animals exhibited fusion. Our findings suggest that b-TCP/DBX can increase both the biochemical stability and biological efficiency of Nell-1 protein.

show abstract

“…ADSCs expressing bone morphogenic proteins have proven effective for spinal fusion in animal models of metabolic bone disease [32,33] . In a study comparing MSCs and ADSCs expressing BMP-2 seeded on collagen sponges, fusion rates were encouraging and not significantly different in the two groups of rat models [34] . Due to the relatively easier clinical access to ADSCs in the patient, greater attention to their potential role in spinal fusion is warranted.…”

Section: Spine Fusionmentioning

confidence: 99%

Stem cells for spine surgery

Schroeder

Kueper

Kaplan

et al. 2015

WJSC

View full text Add to dashboard Cite

In the past few years, stem cells have become the focus of research by regenerative medicine professionals and tissue engineers. Embryonic stem cells, although capable of differentiating into cell lineages of all three germ layers, are limited in their utilization due to ethical issues. In contrast, the autologous harvest and subsequent transplantation of adult stem cells from bone marrow, adipose tissue or blood have been experimentally utilized in the treatment of a wide variety of diseases ranging from myocardial infarction to Alzheimer's disease. The physiologic consequences of stem cell transplantation and its impact on functional recovery have been studied in countless animal models and select clinical trials. Unfortunately, the bench to bedside translation of this research has been slow. Nonetheless, stem cell therapy has received the attention of spinal surgeons due to its potential benefits in the treatment of neural damage, muscle trauma, disk degeneration and its potential contribution to bone fusion.

show abstract

Comparison of Human Mesenchymal Stem Cells Derived From Adipose Tissue and Bone Marrow for Ex Vivo Gene Therapy in Rat Spinal Fusion Model

Cited by 92 publications

References 28 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

Delivery of Lyophilized Nell-1 in a Rat Spinal Fusion Model

Stem cells for spine surgery

Contact Info

Product

Resources

About