An investigation into the use of human bone marrow osteogenic cells in the treatment of bone defects

Timothy Doyle, David Gibson, Susan Clarke, Grant Jordan

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Abstract

Introduction Problematic bone defects are encountered regularly in orthopaedic practice particularly in fracture non-union, revision hip and knee arthroplasty, following bone tumour excision and in spinal fusion surgery. At present the optimal source of graft to ‘fill’ these defects is autologous bone but this has significant drawbacks including harvest site morbidity and limited quantities. Bone marrow has been proposed as the main source of osteogenic stem cells for the tissue-engineered cell therapy approach to bone defect management. Such cells constitute a minute proportion of the total marrow cell population and their isolation and expansion is a time consuming and expensive strategy. In this study we investigated human bone marrow stem cells as a potential treatment of bone defect by looking at variability in patient osteogenic cell populations as a function of patient differences. We produced a model to predict which patients would be more suited to cell based therapies and propose possible methods for improving the quality of grafts. Methods Bone marrow was harvested from 30 patients undergoing elective total hip replacement surgery in Musgrave Park Hospital, Belfast (12 males, 18 females, age range 52-82 years). The osteogenic stem cell fraction was cultured and subsequently analysed using colony forming efficiency assays, flow cytometry, fluorescence activated cell sorting and proteomics. Results The number and proliferative capacity of osteogenic stem cells varied markedly between patients. Statistical analysis revealed significantly better osteogenic capacity in: •male patients•samples in which the growth hormone Fibroblastic Growth Factor-2 was added to culture medium•patients who used the cholesterol lowering agent simvastatinPatient use of inhaled steroids and NSAIDs were found to have detrimental effects. A statistical model to predict marrow profiles based on these variables was produced. Conclusions Stem cell based tissue engineering represents the future of the treatment of bone defect. This study provides evidence that inter-patient variability in marrow cell colony forming and proliferation ability can in some way be explained by patient associated factors. Using this knowledge, we can identify which patients would be best suited to this method of treatment and propose techniques for enhancement of their graft profiles.
LanguageEnglish
Title of host publicationUnknown Host Publication
Pages042
Number of pages2
Volume94-B
Publication statusPublished - 2012
EventBritish Orthopaedic Research Society (BORS) - Cardiff, Wales, 12 - 13 July 2010
Duration: 1 Jan 2012 → …

Conference

ConferenceBritish Orthopaedic Research Society (BORS)
Period1/01/12 → …

Fingerprint

Bone Marrow Cells
Bone and Bones
Stem Cells
Bone Marrow
Therapeutics
Cell- and Tissue-Based Therapy
Immunologic Graft Enhancement
Flow Cytometry
Transplants
Knee Replacement Arthroplasties
Spinal Fusion
Hip Replacement Arthroplasties
Statistical Models
Non-Steroidal Anti-Inflammatory Agents
Tissue Engineering
Proteomics
Population
Growth Hormone
Orthopedics
Culture Media

Keywords

  • Stem cell
  • bone marrow
  • proteomics
  • hip replacement

Cite this

Doyle, T., Gibson, D., Clarke, S., & Jordan, G. (2012). An investigation into the use of human bone marrow osteogenic cells in the treatment of bone defects. In Unknown Host Publication (Vol. 94-B, pp. 042)
Doyle, Timothy ; Gibson, David ; Clarke, Susan ; Jordan, Grant. / An investigation into the use of human bone marrow osteogenic cells in the treatment of bone defects. Unknown Host Publication. Vol. 94-B 2012. pp. 042
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Doyle, T, Gibson, D, Clarke, S & Jordan, G 2012, An investigation into the use of human bone marrow osteogenic cells in the treatment of bone defects. in Unknown Host Publication. vol. 94-B, pp. 042, British Orthopaedic Research Society (BORS), 1/01/12.

An investigation into the use of human bone marrow osteogenic cells in the treatment of bone defects. / Doyle, Timothy; Gibson, David; Clarke, Susan; Jordan, Grant.

Unknown Host Publication. Vol. 94-B 2012. p. 042.

Research output: Chapter in Book/Report/Conference proceedingConference contribution

TY - GEN

T1 - An investigation into the use of human bone marrow osteogenic cells in the treatment of bone defects

AU - Doyle, Timothy

AU - Gibson, David

AU - Clarke, Susan

AU - Jordan, Grant

PY - 2012

Y1 - 2012

N2 - Introduction Problematic bone defects are encountered regularly in orthopaedic practice particularly in fracture non-union, revision hip and knee arthroplasty, following bone tumour excision and in spinal fusion surgery. At present the optimal source of graft to ‘fill’ these defects is autologous bone but this has significant drawbacks including harvest site morbidity and limited quantities. Bone marrow has been proposed as the main source of osteogenic stem cells for the tissue-engineered cell therapy approach to bone defect management. Such cells constitute a minute proportion of the total marrow cell population and their isolation and expansion is a time consuming and expensive strategy. In this study we investigated human bone marrow stem cells as a potential treatment of bone defect by looking at variability in patient osteogenic cell populations as a function of patient differences. We produced a model to predict which patients would be more suited to cell based therapies and propose possible methods for improving the quality of grafts. Methods Bone marrow was harvested from 30 patients undergoing elective total hip replacement surgery in Musgrave Park Hospital, Belfast (12 males, 18 females, age range 52-82 years). The osteogenic stem cell fraction was cultured and subsequently analysed using colony forming efficiency assays, flow cytometry, fluorescence activated cell sorting and proteomics. Results The number and proliferative capacity of osteogenic stem cells varied markedly between patients. Statistical analysis revealed significantly better osteogenic capacity in: •male patients•samples in which the growth hormone Fibroblastic Growth Factor-2 was added to culture medium•patients who used the cholesterol lowering agent simvastatinPatient use of inhaled steroids and NSAIDs were found to have detrimental effects. A statistical model to predict marrow profiles based on these variables was produced. Conclusions Stem cell based tissue engineering represents the future of the treatment of bone defect. This study provides evidence that inter-patient variability in marrow cell colony forming and proliferation ability can in some way be explained by patient associated factors. Using this knowledge, we can identify which patients would be best suited to this method of treatment and propose techniques for enhancement of their graft profiles.

AB - Introduction Problematic bone defects are encountered regularly in orthopaedic practice particularly in fracture non-union, revision hip and knee arthroplasty, following bone tumour excision and in spinal fusion surgery. At present the optimal source of graft to ‘fill’ these defects is autologous bone but this has significant drawbacks including harvest site morbidity and limited quantities. Bone marrow has been proposed as the main source of osteogenic stem cells for the tissue-engineered cell therapy approach to bone defect management. Such cells constitute a minute proportion of the total marrow cell population and their isolation and expansion is a time consuming and expensive strategy. In this study we investigated human bone marrow stem cells as a potential treatment of bone defect by looking at variability in patient osteogenic cell populations as a function of patient differences. We produced a model to predict which patients would be more suited to cell based therapies and propose possible methods for improving the quality of grafts. Methods Bone marrow was harvested from 30 patients undergoing elective total hip replacement surgery in Musgrave Park Hospital, Belfast (12 males, 18 females, age range 52-82 years). The osteogenic stem cell fraction was cultured and subsequently analysed using colony forming efficiency assays, flow cytometry, fluorescence activated cell sorting and proteomics. Results The number and proliferative capacity of osteogenic stem cells varied markedly between patients. Statistical analysis revealed significantly better osteogenic capacity in: •male patients•samples in which the growth hormone Fibroblastic Growth Factor-2 was added to culture medium•patients who used the cholesterol lowering agent simvastatinPatient use of inhaled steroids and NSAIDs were found to have detrimental effects. A statistical model to predict marrow profiles based on these variables was produced. Conclusions Stem cell based tissue engineering represents the future of the treatment of bone defect. This study provides evidence that inter-patient variability in marrow cell colony forming and proliferation ability can in some way be explained by patient associated factors. Using this knowledge, we can identify which patients would be best suited to this method of treatment and propose techniques for enhancement of their graft profiles.

KW - Stem cell

KW - bone marrow

KW - proteomics

KW - hip replacement

M3 - Conference contribution

VL - 94-B

SP - 042

BT - Unknown Host Publication

ER -

Doyle T, Gibson D, Clarke S, Jordan G. An investigation into the use of human bone marrow osteogenic cells in the treatment of bone defects. In Unknown Host Publication. Vol. 94-B. 2012. p. 042