Percutaneous Autologous Bone-Marrow Grafting for Nonunions: Influence of the Number and Concentration of Progenitor Cells

BackgroundBone marrow aspirated from the iliac crest contains progenitor cells that can be used to obtain bone-healing of nonunions. However, there is little available information regarding the number and concentration of these cells that are necessary to obtain bone repair. The purpose of this stud...

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Published in:Journal of bone and joint surgery. American volume 2005-07, Vol.87 (7), p.1430-1437
Main Authors: Hernigou, Ph, Poignard, A, Beaujean, F, Rouard, H
Format: Article
Language:English
Subjects:
Adult
Biological and medical sciences
Bone Marrow Transplantation
Bony Callus - physiology
Cell Count
Diaphyses
Diseases of the osteoarticular system
Female
Fracture Healing - physiology
Fractures, Ununited - diagnostic imaging
Fractures, Ununited - therapy
Humans
Male
Medical sciences
Middle Aged
Orthopedic surgery
Osteogenesis - physiology
Stem Cells
Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases
Tibial Fractures - diagnostic imaging
Tibial Fractures - therapy
Tomography, X-Ray Computed
Treatment Outcome
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container_title Journal of bone and joint surgery. American volume
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creator Hernigou, Ph
Poignard, A
Beaujean, F
Rouard, H
description BackgroundBone marrow aspirated from the iliac crest contains progenitor cells that can be used to obtain bone-healing of nonunions. However, there is little available information regarding the number and concentration of these cells that are necessary to obtain bone repair. The purpose of this study was to evaluate the number and concentration of progenitor cells that were transplanted for the treatment of nonunion, the callus volume obtained after the transplantation, and the clinical healing rate.MethodsMarrow was aspirated from both anterior iliac crests, concentrated on a cell separator, and then injected into sixty noninfected atrophic nonunions of the tibia. Each nonunion received a relatively constant volume of 20 cm of concentrated bone marrow. The number of progenitor cells that was transplanted was estimated by counting the fibroblast colony-forming units. The volume of mineralized bone formation was determined by comparing preoperative computerized tomography scans with scans performed four months following the injection.ResultsThe aspirates contained an average (and standard deviation) of 612 ± 134 progenitors/cm (range, 12 to 1224 progenitors/cm) before concentration and an average of 2579 ± 1121 progenitors/cm (range, 60 to 6120 progenitors/cm) after concentration. An average total of 51 × 10 fibroblast colony-forming units was injected into each nonunion. Bone union was obtained in fifty-three patients, and the bone marrow that had been injected into the nonunions of those patients contained >1500 progenitors/cm and an average total of 54,962 ± 17,431 progenitors. The concentration (634 ± 187 progenitors/cm) and the total number (19,324 ± 6843) of progenitors injected into the nonunion sites of the seven patients in whom bone union was not obtained were both significantly lower (p = 0.001 and p < 0.01, respectively) than those in the patients who obtained bone union. The volume of the mineralized callus measured at four months on the computerized tomography scans of the patients who had union ranged from 0.8 to 5.3 cm (mean, 3.1 cm). There was a positive correlation between the volume of mineralized callus at four months and the number (p = 0.04) and concentration (p = 0.01) of fibroblast colony-forming units in the graft. There was a negative correlation between the time needed to obtain union and the concentration of fibroblast colony-forming units in the graft (p = 0.04).ConclusionsPercutaneous autologous bone-marrow grafting is an effec
doi_str_mv 10.2106/JBJS.D.02215
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However, there is little available information regarding the number and concentration of these cells that are necessary to obtain bone repair. The purpose of this study was to evaluate the number and concentration of progenitor cells that were transplanted for the treatment of nonunion, the callus volume obtained after the transplantation, and the clinical healing rate.MethodsMarrow was aspirated from both anterior iliac crests, concentrated on a cell separator, and then injected into sixty noninfected atrophic nonunions of the tibia. Each nonunion received a relatively constant volume of 20 cm of concentrated bone marrow. The number of progenitor cells that was transplanted was estimated by counting the fibroblast colony-forming units. The volume of mineralized bone formation was determined by comparing preoperative computerized tomography scans with scans performed four months following the injection.ResultsThe aspirates contained an average (and standard deviation) of 612 ± 134 progenitors/cm (range, 12 to 1224 progenitors/cm) before concentration and an average of 2579 ± 1121 progenitors/cm (range, 60 to 6120 progenitors/cm) after concentration. An average total of 51 × 10 fibroblast colony-forming units was injected into each nonunion. Bone union was obtained in fifty-three patients, and the bone marrow that had been injected into the nonunions of those patients contained &gt;1500 progenitors/cm and an average total of 54,962 ± 17,431 progenitors. The concentration (634 ± 187 progenitors/cm) and the total number (19,324 ± 6843) of progenitors injected into the nonunion sites of the seven patients in whom bone union was not obtained were both significantly lower (p = 0.001 and p &lt; 0.01, respectively) than those in the patients who obtained bone union. The volume of the mineralized callus measured at four months on the computerized tomography scans of the patients who had union ranged from 0.8 to 5.3 cm (mean, 3.1 cm). There was a positive correlation between the volume of mineralized callus at four months and the number (p = 0.04) and concentration (p = 0.01) of fibroblast colony-forming units in the graft. There was a negative correlation between the time needed to obtain union and the concentration of fibroblast colony-forming units in the graft (p = 0.04).ConclusionsPercutaneous autologous bone-marrow grafting is an effective and safe method for the treatment of an atrophic tibial diaphyseal nonunion. However, its efficacy appears to be related to the number of progenitors in the graft, and the number of progenitors available in bone marrow aspirated from the iliac crest appears to be less than optimal in the absence of concentration.Level of EvidenceTherapeutic Level III. See Instructions to Authors for a complete description of levels of evidence.</description><edition>American volume</edition><identifier>ISSN: 0021-9355</identifier><identifier>EISSN: 1535-1386</identifier><identifier>DOI: 10.2106/JBJS.D.02215</identifier><identifier>PMID: 15995108</identifier><identifier>CODEN: JBJSA3</identifier><language>eng</language><publisher>Boston, MA: Copyright by The Journal of Bone and Joint Surgery, Incorporated</publisher><subject>Adult ; Biological and medical sciences ; Bone Marrow Transplantation ; Bony Callus - physiology ; Cell Count ; Diaphyses ; Diseases of the osteoarticular system ; Female ; Fracture Healing - physiology ; Fractures, Ununited - diagnostic imaging ; Fractures, Ununited - therapy ; Humans ; Male ; Medical sciences ; Middle Aged ; Orthopedic surgery ; Osteogenesis - physiology ; Stem Cells ; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases ; Tibial Fractures - diagnostic imaging ; Tibial Fractures - therapy ; Tomography, X-Ray Computed ; Treatment Outcome</subject><ispartof>Journal of bone and joint surgery. American volume, 2005-07, Vol.87 (7), p.1430-1437</ispartof><rights>Copyright 2005 by The Journal of Bone and Joint Surgery, Incorporated</rights><rights>2005 INIST-CNRS</rights><rights>Copyright Journal of Bone and Joint Surgery, Inc. Jul 2005</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5313-7709536142d24e67c8c94d21b27d44bc9d21514b15b25417763f42eedf714d733</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,786,790,27957,27958</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&amp;idt=16974170$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15995108$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hernigou, Ph</creatorcontrib><creatorcontrib>Poignard, A</creatorcontrib><creatorcontrib>Beaujean, F</creatorcontrib><creatorcontrib>Rouard, H</creatorcontrib><title>Percutaneous Autologous Bone-Marrow Grafting for Nonunions: Influence of the Number and Concentration of Progenitor Cells</title><title>Journal of bone and joint surgery. American volume</title><addtitle>J Bone Joint Surg Am</addtitle><description>BackgroundBone marrow aspirated from the iliac crest contains progenitor cells that can be used to obtain bone-healing of nonunions. However, there is little available information regarding the number and concentration of these cells that are necessary to obtain bone repair. The purpose of this study was to evaluate the number and concentration of progenitor cells that were transplanted for the treatment of nonunion, the callus volume obtained after the transplantation, and the clinical healing rate.MethodsMarrow was aspirated from both anterior iliac crests, concentrated on a cell separator, and then injected into sixty noninfected atrophic nonunions of the tibia. Each nonunion received a relatively constant volume of 20 cm of concentrated bone marrow. The number of progenitor cells that was transplanted was estimated by counting the fibroblast colony-forming units. The volume of mineralized bone formation was determined by comparing preoperative computerized tomography scans with scans performed four months following the injection.ResultsThe aspirates contained an average (and standard deviation) of 612 ± 134 progenitors/cm (range, 12 to 1224 progenitors/cm) before concentration and an average of 2579 ± 1121 progenitors/cm (range, 60 to 6120 progenitors/cm) after concentration. An average total of 51 × 10 fibroblast colony-forming units was injected into each nonunion. Bone union was obtained in fifty-three patients, and the bone marrow that had been injected into the nonunions of those patients contained &gt;1500 progenitors/cm and an average total of 54,962 ± 17,431 progenitors. The concentration (634 ± 187 progenitors/cm) and the total number (19,324 ± 6843) of progenitors injected into the nonunion sites of the seven patients in whom bone union was not obtained were both significantly lower (p = 0.001 and p &lt; 0.01, respectively) than those in the patients who obtained bone union. The volume of the mineralized callus measured at four months on the computerized tomography scans of the patients who had union ranged from 0.8 to 5.3 cm (mean, 3.1 cm). There was a positive correlation between the volume of mineralized callus at four months and the number (p = 0.04) and concentration (p = 0.01) of fibroblast colony-forming units in the graft. There was a negative correlation between the time needed to obtain union and the concentration of fibroblast colony-forming units in the graft (p = 0.04).ConclusionsPercutaneous autologous bone-marrow grafting is an effective and safe method for the treatment of an atrophic tibial diaphyseal nonunion. However, its efficacy appears to be related to the number of progenitors in the graft, and the number of progenitors available in bone marrow aspirated from the iliac crest appears to be less than optimal in the absence of concentration.Level of EvidenceTherapeutic Level III. See Instructions to Authors for a complete description of levels of evidence.</description><subject>Adult</subject><subject>Biological and medical sciences</subject><subject>Bone Marrow Transplantation</subject><subject>Bony Callus - physiology</subject><subject>Cell Count</subject><subject>Diaphyses</subject><subject>Diseases of the osteoarticular system</subject><subject>Female</subject><subject>Fracture Healing - physiology</subject><subject>Fractures, Ununited - diagnostic imaging</subject><subject>Fractures, Ununited - therapy</subject><subject>Humans</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Orthopedic surgery</subject><subject>Osteogenesis - physiology</subject><subject>Stem Cells</subject><subject>Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases</subject><subject>Tibial Fractures - diagnostic imaging</subject><subject>Tibial Fractures - therapy</subject><subject>Tomography, X-Ray Computed</subject><subject>Treatment Outcome</subject><issn>0021-9355</issn><issn>1535-1386</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><recordid>eNqFks1v1DAQxS0EokvhxhlZSHAiy_g76a3dQmlVSiXgbDmJs5uStYs_tOp_j8OuVIkLJ4_HP43em2eEXhNYUgLy49XZ1ffl-RIoJeIJWhDBREVYLZ-iBQAlVcOEOEIvYrwDAM5BPUdHRDSNIFAv0MOtDV1OxlmfIz7NyU9-PZdn3tnqqwnB7_BFMEMa3RoPPuAb77IbvYsn-NINU7aus9gPOG0svsnb1gZsXI9XvvRdCiYVdn6_DX5t3ZjKiJWdpvgSPRvMFO2rw3mMfn7-9GP1pbr-dnG5Or2uOsEIq5SCRjBJOO0pt1J1ddfwnpKWqp7ztmtKLQhviWip4EQpyQZOre0HRXivGDtG7_dz74P_nW1MejvGrijYe9ayBiASyH9BospWJUAB3_4D3vkcXDGhKQioiZJNgT7soS74GIMd9H0YtyY8aAJ6Dk7Pwelz_Te4gr85zMzt1vaP8CGpArw7ACZ2ZhqCcd0YHznZqOJ-Fsf33M5PyYb4a8o7G_TGmiltNMx_QFJWUShKVblVc4uxPzZArtA</recordid><startdate>200507</startdate><enddate>200507</enddate><creator>Hernigou, Ph</creator><creator>Poignard, A</creator><creator>Beaujean, F</creator><creator>Rouard, H</creator><general>Copyright by The Journal of Bone and Joint Surgery, Incorporated</general><general>Journal of Bone and Joint Surgery Incorporated</general><general>Journal of Bone and Joint Surgery AMERICAN VOLUME</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QL</scope><scope>7QO</scope><scope>7QP</scope><scope>7RV</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88I</scope><scope>8AF</scope><scope>8FD</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7N</scope><scope>NAPCQ</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>7X8</scope></search><sort><creationdate>200507</creationdate><title>Percutaneous Autologous Bone-Marrow Grafting for Nonunions: Influence of the Number and Concentration of Progenitor Cells</title><author>Hernigou, Ph ; Poignard, A ; Beaujean, F ; Rouard, H</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5313-7709536142d24e67c8c94d21b27d44bc9d21514b15b25417763f42eedf714d733</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Adult</topic><topic>Biological and medical sciences</topic><topic>Bone Marrow Transplantation</topic><topic>Bony Callus - physiology</topic><topic>Cell Count</topic><topic>Diaphyses</topic><topic>Diseases of the osteoarticular system</topic><topic>Female</topic><topic>Fracture Healing - physiology</topic><topic>Fractures, Ununited - diagnostic imaging</topic><topic>Fractures, Ununited - therapy</topic><topic>Humans</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Orthopedic surgery</topic><topic>Osteogenesis - physiology</topic><topic>Stem Cells</topic><topic>Surgery (general aspects). Transplantations, organ and tissue grafts. 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American volume</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hernigou, Ph</au><au>Poignard, A</au><au>Beaujean, F</au><au>Rouard, H</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Percutaneous Autologous Bone-Marrow Grafting for Nonunions: Influence of the Number and Concentration of Progenitor Cells</atitle><jtitle>Journal of bone and joint surgery. American volume</jtitle><addtitle>J Bone Joint Surg Am</addtitle><date>2005-07</date><risdate>2005</risdate><volume>87</volume><issue>7</issue><spage>1430</spage><epage>1437</epage><pages>1430-1437</pages><issn>0021-9355</issn><eissn>1535-1386</eissn><coden>JBJSA3</coden><notes>ObjectType-Article-1</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-2</notes><notes>content type line 23</notes><abstract>BackgroundBone marrow aspirated from the iliac crest contains progenitor cells that can be used to obtain bone-healing of nonunions. However, there is little available information regarding the number and concentration of these cells that are necessary to obtain bone repair. The purpose of this study was to evaluate the number and concentration of progenitor cells that were transplanted for the treatment of nonunion, the callus volume obtained after the transplantation, and the clinical healing rate.MethodsMarrow was aspirated from both anterior iliac crests, concentrated on a cell separator, and then injected into sixty noninfected atrophic nonunions of the tibia. Each nonunion received a relatively constant volume of 20 cm of concentrated bone marrow. The number of progenitor cells that was transplanted was estimated by counting the fibroblast colony-forming units. The volume of mineralized bone formation was determined by comparing preoperative computerized tomography scans with scans performed four months following the injection.ResultsThe aspirates contained an average (and standard deviation) of 612 ± 134 progenitors/cm (range, 12 to 1224 progenitors/cm) before concentration and an average of 2579 ± 1121 progenitors/cm (range, 60 to 6120 progenitors/cm) after concentration. An average total of 51 × 10 fibroblast colony-forming units was injected into each nonunion. Bone union was obtained in fifty-three patients, and the bone marrow that had been injected into the nonunions of those patients contained &gt;1500 progenitors/cm and an average total of 54,962 ± 17,431 progenitors. The concentration (634 ± 187 progenitors/cm) and the total number (19,324 ± 6843) of progenitors injected into the nonunion sites of the seven patients in whom bone union was not obtained were both significantly lower (p = 0.001 and p &lt; 0.01, respectively) than those in the patients who obtained bone union. The volume of the mineralized callus measured at four months on the computerized tomography scans of the patients who had union ranged from 0.8 to 5.3 cm (mean, 3.1 cm). There was a positive correlation between the volume of mineralized callus at four months and the number (p = 0.04) and concentration (p = 0.01) of fibroblast colony-forming units in the graft. There was a negative correlation between the time needed to obtain union and the concentration of fibroblast colony-forming units in the graft (p = 0.04).ConclusionsPercutaneous autologous bone-marrow grafting is an effective and safe method for the treatment of an atrophic tibial diaphyseal nonunion. However, its efficacy appears to be related to the number of progenitors in the graft, and the number of progenitors available in bone marrow aspirated from the iliac crest appears to be less than optimal in the absence of concentration.Level of EvidenceTherapeutic Level III. See Instructions to Authors for a complete description of levels of evidence.</abstract><cop>Boston, MA</cop><pub>Copyright by The Journal of Bone and Joint Surgery, Incorporated</pub><pmid>15995108</pmid><doi>10.2106/JBJS.D.02215</doi><tpages>8</tpages><edition>American volume</edition></addata></record>
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subjects Adult
Biological and medical sciences
Bone Marrow Transplantation
Bony Callus - physiology
Cell Count
Diaphyses
Diseases of the osteoarticular system
Female
Fracture Healing - physiology
Fractures, Ununited - diagnostic imaging
Fractures, Ununited - therapy
Humans
Male
Medical sciences
Middle Aged
Orthopedic surgery
Osteogenesis - physiology
Stem Cells
Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases
Tibial Fractures - diagnostic imaging
Tibial Fractures - therapy
Tomography, X-Ray Computed
Treatment Outcome
title Percutaneous Autologous Bone-Marrow Grafting for Nonunions: Influence of the Number and Concentration of Progenitor Cells
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