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Use of adipose tissue-derived stromal cells in spinal fusion

Inactive Publication Date: 2007-02-01
BOARD OF SUPERVISORS OF LOUISIANA STATE UNIV & AGRI & MECHANICAL COLLEGE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0009] The invention includes a method of enhancing the fusion of bone following a spinal fusion procedure in a mammal comprising administering an isolated adipose tissue-der

Problems solved by technology

The repair of large segmental defects in diaphyseal bone is a significant problem faced by orthopaedic surgeons today.
The use of fresh autologous bone graft material has been viewed as the historical standard of treatment but is associated with substantial morbidity including infection, malformation, pain, and loss of function (Kahn et al., 1995, Clin. Orthop. Rel. Res. 313:69-75).
Although widely used for many years, the risk of disease transmission, host rejection, and lack of osteoinduction compromise its desirability (Leads, 1988, JAMA 260:2487-2488).
The favorably porous nature of these implants facilitate bony ingrowth, but their lack of osteoinductive potential limits their utility.
Though sound in principle, the practicality of obtaining enough bone marrow with the requisite number of osteoprogenitor cells is limiting.

Method used

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  • Use of adipose tissue-derived stromal cells in spinal fusion
  • Use of adipose tissue-derived stromal cells in spinal fusion
  • Use of adipose tissue-derived stromal cells in spinal fusion

Examples

Experimental program
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Effect test

example 1

Alternatives to Autograft Bone in Spinal Fusion Surgery

[0160] Over 75% of the American population suffers from back pain. In some instances, underlying medical illnesses can contribute to back pain. These include scoliosis, spinal stenosis, degenerative disc disease, infectious processes, tumors, and trauma. For 1% of the population, the back pain is so severe that they are forced to go onto lifetime disability; an additional 1% of the population is incapacitated by back pain for a limited time period. The majority of the mammals with back pain are treated with conservative therapies; however, when modalities such as bed rest and medication fail, physicians often recommend spinal fusion surgery. The goal of this operation is to form ectopic bone between two or more adjacent vertebra, “fusing” them together into a solid structure. Immobilization of the vertebral joint reduces the pressure on nerve roots leaving the spinal cord and the resulting painful sensation. Surgeons use a post...

example 2

ADAS Cell Osteogenesis In Vitro

[0168] It has been demonstrated that human ADAS cells display an osteogenic phenotype in vitro when cultured in the presence of ascorbate, β-glycerophosphate, dexamethasone, and 1,25 dihydroxyvitamin D3 (Halvorsen et al., 2001, Tissue Eng. 7:729-41). Under these conditions, the ADAS cells mineralize their extracellular matrix as demonstrated by positive staining with either Alizarin Red or von Kossa for calcium phosphate deposition (FIG. 3).

[0169] It was observed that human ADAS cell osteogenesis over a 10-day period was accompanied by an increase in alkaline phosphatase activity. At the end of the culture period, osteogenic cells (mineralized) displayed a 3-fold higher level of alkaline phosphatase relative to cells maintained under control conditions (FIG. 4). Likewise, there was a time dependent increase in secreted levels of osteocalcin protein under osteogenic conditions. The ADAS cells expressed a number of gene markers consistent with an osteo...

example 3

ADAS Cells are Osteogenic In Vivo

[0171] To extend the in vitro findings, human ADAS cells were transplanted into immunodeficient SCID mice. The ADAS cells were loaded onto three cm3 cubes of hydroxyapatite / tricalcium phosphate (HA / TCP) scaffold and implanted subcutaneously. After a 6-week period, the implants were harvested, fixed, decalcified, and stained with Hematoxylin / Eosin or with human nuclear antigen specific antibodies (FIG. 5). Based on H&E staining, it was observed that new bone formed adjacent to the hydroxyapatite / tricalcium phosphate scaffold in the presence of the human ADAS cells. The human cells were identified within the bone based on immunofluorescent analysis with the human antigen specific antibody. In the presence of the scaffold alone (no cells), new bone did not form and no human cells were detected. These studies demonstrate that ADAS cells are capable of osteogenesis in vivo.

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Abstract

The present invention encompasses methods and compositions for treating a bone condition. The isolated adipose tissue-derived stromal cell of the invention and products related thereto have a plethora of uses, including but not limited to research, diagnostic, and therapeutic applications such as in spinal fusion procedures.

Description

BACKGROUND OF THE INVENTION [0001] There generally are two types of bone conditions: 1) non-metabolic bone conditions, such as bone fractures, bone / spinal deformation, osteosarcoma, myeloma, bone dysplasia and scoliosis, and 2) metabolic bone conditions, such as osteoporosis, osteomalacia, rickets, fibrous osteitis, renal bone dystrophy and Paget's disease of bone. Osteoporosis, a metabolic bone condition, is a systemic disease characterized by increased bone fragility and fracturability due to decreased bone mass and change in fine bone tissue structure, its major clinical symptoms including spinal kyphosis, and fractures of dorsolumbar bones, vertebral centra, femoral necks, lower end of radius, ribs, upper end of humerus, and others. In bone tissue, bone formation and destruction due to bone resorption occur constantly. Upon deterioration of the balance between bone formation and bone destruction due to bone resorption, a quantitative reduction in bone occurs. Traditionally, bone...

Claims

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Application Information

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IPC IPC(8): A61F2/44
CPCA61F2/4455A61F2002/30678A61F2002/445A61L27/3608A61L27/3654A61K35/28A61L27/3804A61L27/3852A61L27/3856A61L2430/38A61L27/3658A61F2002/30677A61P19/00A61P19/02A61P19/08A61P19/10A61P25/00A61P43/00A61F2/44
Inventor GIMBLE, JEFFREY M.LOPEZ, MANDI
Owner BOARD OF SUPERVISORS OF LOUISIANA STATE UNIV & AGRI & MECHANICAL COLLEGE
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