Correction: Use of Autologous Human mesenchymal Stromal Cell/Fibrin Clot Constructs in Upper Limb Non-Unions: Long-Term Assessment
Open accessAbstract
Background: Tissue engineering appears to be an attractive alternative to the traditional approach in the treatment of fracture non-unions.Mesenchymal stromal cells (MSCs) are considered an appealing cell source for clinical intervention.However, ex vivo cell expansion and differentiation towards the osteogenic lineage, together with the design of a suitable scaffold have yet to be optimized.Major concerns exist about the safety of MSC-based therapies, including possible abnormal overgrowth and potential cancer evolution. Aims:We examined the long-term efficacy and safety of ex vivo expanded bone marrow MSCs, embedded in autologous fibrin clots, for the healing of atrophic pseudarthrosis of the upper limb.Our research work relied on three main issues: use of an entirely autologous context (cells, serum for ex vivo cell culture, scaffold components), reduced ex vivo cell expansion, and short-term MSC osteoinduction before implantation.Methods and Findings: Bone marrow MSCs isolated from 8 patients were expanded ex vivo until passage 1 and short-term osteo-differentiated in autologous-based culture conditions.Tissue-engineered constructs designed to embed MSCs in autologous fibrin clots were locally implanted with bone grafts, calibrating their number on the extension of bone damage.Radiographic healing was evaluated with short-and long-term follow-ups (range averages: 6.7 and 76.0 months, respectively).All patients recovered limb function, with no evidence of tissue overgrowth or tumor formation.Conclusions: Our study indicates that highly autologous treatment can be effective and safe in the long-term healing of bone non-unions.This tissue engineering approach resulted in successful clinical and functional outcomes for all patients.
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Osteogenically differentiated autologous BM-MSCs within fibrin clots can be safely used to heal non-unions.
“The functional recovery seen through the use of osteogenically differentiated autologous BM-MSCs within fibrin clots shows they can be safely used to heal non-unions [39,93].”
From Mesenchymal Stem/Stromal Cells: Immunomodulatory and Bone Regeneration Potential after Tumor Excision in Osteosarcoma Patients (2023) · cites this paper as [93]
The correction (unpaginated) identifies the work as concerning mesenchymal stromal cell/fibrin-clot constructs in upper-limb non-unions and reports consistent short-term radiographic healing in the patients. It does not report functional recovery, establish that the cells were osteogenically differentiated, or assess safety, so those parts of the claim are unsupported by this copy. (LLM, conf=0.84)
Experimental — accuracy not yet measuredIn Giannotti et al., all eight patients with upper-limb non-union fractures treated with ex vivo expanded BM-MSCs embedded in autologous fibrin clots regained limb function at short and long term follow-ups (average 6.7 and 76 months) with no indications of excessive tissue growth or tumor development.
“At both the short and long term follow-ups at an average time of 6.7 months and 76 months, respectively, all eight of the patients in this study regained the function of their limb with no indications of excessive tissue growth or tumor development.”
From Mesenchymal Stem/Stromal Cells: Immunomodulatory and Bone Regeneration Potential after Tumor Excision in Osteosarcoma Patients (2023) · cites this paper as [93]
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Cites
Multilineage potential of adult human mesenchymal stem cells
Pittenger, M. F., Mackay, A. M., Beck, S. C., Jaiswal, R. K., Douglas, R., Mosca, J. D., Moorman, M. A., Simonetti, D. W., Craig, S., & Marshak, D. R. (1999) · Science · doi:10.1126/science.284.5411.143 · Cited by 21,052 · see citing works
Multilineage Cells from Human Adipose Tissue: Implications for Cell-Based Therapies
Zuk, P. A., Zhu, M., Mizuno, H., Huang, J., Futrell, J. W., Katz, A. J., Benhaim, P., Lorenz, H. P., & Hedrick, M. H. (2001) · Tissue Engineering · doi:10.1089/107632701300062859 · Cited by 7,956 · see citing works
Hydrogels in regenerative medicine
Slaughter, B. V., Khurshid, S. S., Fisher, O. Z., Khademhosseini, A., & Peppas, N. A. (2009) · Advanced Materials · doi:10.1002/adma.200802106 · Cited by 2,703 · see citing works
Stem Cell Properties of Human Dental Pulp Stem Cells
Gronthos, S., Brahim, J. S., Li, W., Fisher, L. W., Cherman, N., BOYDE, A., DenBesten, P., Robey, P. G., & Shi, S. (2002) · Journal of Dental Research · doi:10.1177/154405910208100806 · Cited by 2,115 · see citing works
Horwitz, E. M., Blanc, K. L., Dominici, M., Mueller, I., Slaper‐Cortenbach, I., Marini, F. C., Deans, R. J., Krause, D. S., & Keating, A. (2005) · Cytotherapy · doi:10.1080/14653240500319234 · Cited by 2,074 · see citing works
The Comprehensive Classification of Fractures of Long Bones
Müller, M. E., Koch, P. M., Nazarian, S., & Schatzker, J. (1990) · Springer eBooks · doi:10.1007/978-3-642-61261-9 · Cited by 2,050 · see citing works
Repair of Large Bone Defects with the Use of Autologous Bone Marrow Stromal Cells
Quarto, R., Mastrogiacomo, M., Cancedda, R., Кутепов, С. М., Mukhachev, V., Lavroukov, A., Kon, E., & Marcacci, M. (2001) · New England Journal of Medicine · doi:10.1056/nejm200102013440516 · Cited by 1,382 · see citing works
Fracture healing: The diamond concept
Giannoudis, P. V., Einhorn, T. A., & Marsh, D. (2007) · Injury · doi:10.1016/s0020-1383(08)70003-2 · Cited by 1,092 · see citing works
Fibrin: A versatile scaffold for tissue engineering applications
Ahmed, T. A. E., Dare, E. V., & Hincke, M. (2008) · Tissue Engineering Part B: Reviews · doi:10.1089/ten.teb.2007.0435 · Cited by 994 · see citing works
Aging of mesenchymal stem cell in vitro
Bonab, M. M., Alimoghaddam, K., Talebian, F., Ghaffari, S. H., Ghavamzadeh, A., & Nikbin, B. (2006) · BMC Cell Biology · doi:10.1186/1471-2121-7-14 · Cited by 888 · see citing works
Marcacci, M., Kon, E., Moukhachev, V., Lavroukov, A., Kutepov, S., Quarto, R., Mastrogiacomo, M., & Cancedda, R. (2007) · Tissue Engineering · doi:10.1089/ten.2006.0271 · Cited by 589 · see citing works
ALLOGENEIC MESENCHYMAL STEM CELLS REGENERATE BONE IN A CRITICAL-SIZED CANINE SEGMENTAL DEFECT
Arinzeh, T. L., Peter, S. J., Archambault, M., van den Bos, C., GORDON, S., Kraus, K. H., SMITH, A., & Kadiyala, S. (2003) · Journal of Bone and Joint Surgery · doi:10.2106/00004623-200310000-00010 · Cited by 503 · see citing works
Fibrin gel – advantages of a new scaffold in cardiovascular tissue engineering
Jockenhoevel, S., Zünd, G., Hoerstrup, S. P., Chalabi, K., Sachweh, J. S., Demircan, L., Messmer, B. J., & Turina, M. I. (2001) · European Journal of Cardio-Thoracic Surgery · doi:10.1016/s1010-7940(01)00624-8 · Cited by 362 · see citing works
Cross-Linking Exogenous Bifunctional Peptides into Fibrin Gels with Factor XIIIa
Schense, J. C., & Hubbell, J. A. (1998) · Bioconjugate Chemistry · doi:10.1021/bc9800769 · Cited by 311 · see citing works
Engineering of fibrin-based functional and implantable small-diameter blood vessels
Swartz, D. D., Russell, J. A., & Andreadis, S. T. (2004) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00479.2004 · Cited by 277 · see citing works
The health economics of the treatment of long-bone non-unions
Kanakaris, N. K., & Giannoudis, P. V. (2007) · Injury · doi:10.1016/s0020-1383(07)80012-x · Cited by 256 · see citing works
Pacini, S., Spinabella, S., Trombi, L., Fazzi, R., Galimberti, S., Dini, F., Carlucci, F., & Petrini, M. (2007) · Tissue Engineering · doi:10.1089/ten.2007.0108 · Cited by 233 · see citing works
Self-citationSpine Fusion Using Cell Matrix Composites Enriched in Bone Marrow-Derived Cells
Muschler, G. F., Nitto, H., Matsukura, Y., Boehm, C., Valdevit, A. D. C., KAMBIC, H. E., Davros, W. J., Powell, K. A., & Easley, K. A. (2003) · Clinical Orthopaedics and Related Research · doi:10.1097/00003086-200302000-00018 · Cited by 203 · see citing works
Femoral Nonunion: Risk Factors and Treatment Options
Lynch, J. R., Taitsman, L. A., Barei, D. P., & Nork, S. E. (2008) · Journal of the American Academy of Orthopaedic Surgeons · doi:10.5435/00124635-200802000-00006 · Cited by 166 · see citing works
Bone regeneration: stem cell therapies and clinical studies in orthopaedics and traumatology
Gómez‐Barrena, E., Rosset, P., Müller, I., Giordano, R., Bunu, C., Layrolle, P., Konttinen, Y. T., & Luyten, F. P. (2011) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2011.01265.x · Cited by 149 · see citing works
Veronesi, F., Giavaresi, G., Tschon, M., Borsari, V., Aldini, N. N., & Fini, M. (2012) · Stem Cells and Development · doi:10.1089/scd.2012.0373 · Cited by 148 · see citing works
Bone Marrow Concentrate: A Novel Strategy for Bone Defect Treatment
Jäger, M., Jelinek, E. M., Wess, K. M., Scharfstädt, A., Jacobson, M. S., Kevy, S. V., & Krauspe, R. (2009) · Current Stem Cell Research & Therapy · doi:10.2174/157488809787169039 · Cited by 147 · see citing works
Cell Therapy for Bone Disease: A Review of Current Status
Cancedda, R., Bianchi, G., Derubeis, A. R., & Quarto, R. (2003) · Stem Cells · doi:10.1634/stemcells.21-5-610 · Cited by 146 · see citing works
Seebach, C., Schultheiss, J., Wilhelm, K., Frank, J. M., & Henrich, D. M. (2010) · Injury · doi:10.1016/j.injury.2010.02.017 · Cited by 143 · see citing works
Kassem, M. S., & Abdallah, B. M. (2007) · Cell and Tissue Research · doi:10.1007/s00441-007-0509-0 · Cited by 137 · see citing works
Human mesenchymal stem cells and their use in cell‐based therapies
Motaln, H., Schichor, C., & Lah, T. T. (2010) · Cancer · doi:10.1002/cncr.25056 · Cited by 129 · see citing works
Schwartz, C. E., Martha, J. F., Kowalski, P., Wang, D. A., Bode, R. K., Li, L., & Kim, D. H. (2009) · Health and Quality of Life Outcomes · doi:10.1186/1477-7525-7-49 · Cited by 128 · see citing works
Bajada, S., Harrison, P. E., Ashton, B. A., Cassar‐Pullicino, V. N., Ashammakhi, N. A., & Richardson, J. B. (2007) · Journal of Bone and Joint Surgery - British Volume · doi:10.1302/0301-620x.89b10.19103 · Cited by 118 · see citing works
Kim, S.-J., Shin, Y.-W., Yang, K.-H., Kim, S.-B., Yoo, M.-J., Han, S.-K., Im, S.-A., Won, Y.-D., Sung, Y.-B., Jeon, T.-S., et al. (2009) · BMC Musculoskeletal Disorders · doi:10.1186/1471-2474-10-20 · Cited by 111 · see citing works
Application of Stem Cells in Orthopedics
Schmitt, A., van Griensven, M., Imhoff, A. B., & Buchmann, S. (2012) · Stem Cells International · doi:10.1155/2012/394962 · Cited by 96 · see citing works
Butler, D. L., Gooch, C., Kinneberg, K. R. C., Boivin, G. P., Galloway, M. T., Nirmalanandhan, V. S., Shearn, J. T., Dyment, N. A., & Juncosa‐Melvin, N. (2010) · Nature Protocols · doi:10.1038/nprot.2010.14 · Cited by 90 · see citing works
Vascularised bone grafts for the management of non-union
Soucacos, P. N., Dailiana, Z. H., Beris, A. E., & Johnson, E. O. (2006) · Injury · doi:10.1016/j.injury.2006.02.040 · Cited by 85 · see citing works
Fibrin glue as the cell-delivery vehicle for mesenchymal stromal cells in regenerative medicine
Wu, X., Ren, J., & Li, J. (2011) · Cytotherapy · doi:10.3109/14653249.2011.638914 · Cited by 80 · see citing works
Defining human mesenchymal stem cell efficacy in vivo
Bonfield, T. L., Nolan, M., Lennon, D. P., & Caplan, A. I. (2010) · Journal of Inflammation · doi:10.1186/1476-9255-7-51 · Cited by 80 · see citing works
Shearn, J. T., Juncosa‐Melvin, N., Boivin, G. P., Galloway, M. T., Goodwin, W., Gooch, C., Dunn, M. G., & Butler, D. L. (2007) · Journal of Biomechanical Engineering · doi:10.1115/1.2800769 · Cited by 79 · see citing works
Mesenchymal Stem Cells in drug/gene Delivery: Implications for Cell Therapy
Greco, S. J., & Rameshwar, P. (2012) · Therapeutic Delivery · doi:10.4155/tde.12.69 · Cited by 68 · see citing works
Barachini, S., Trombi, L., Danti, S., D’Alessandro, D., Battolla, B., Legitimo, A., Nesti, C., Mucci, I., D’Acunto, M., Cascone, M. G., et al. (2008) · Stem Cells and Development · doi:10.1089/scd.2008.0017 · Cited by 56 · see citing works
Self-citationConstitutive Expression of Pluripotency-Associated Genes in Mesodermal Progenitor Cells (MPCs)
Pacini, S., Carnicelli, V., Trombi, L., Montali, M., Fazzi, R., Lazzarini, E., Giannotti, S., & Petrini, M. (2010) · PLoS ONE · doi:10.1371/journal.pone.0009861 · Cited by 52 · see citing works
Self-citationIdentification and Purification of Mesodermal Progenitor Cells From Human Adult Bone Marrow
Petrini, M., Pacini, S., Trombi, L., Fazzi, R., Montali, M., Ikehara, S., & Abraham, N. G. (2008) · Stem Cells and Development · doi:10.1089/scd.2008.0291 · Cited by 52 · see citing works
Self-citationKitoh, H., Kawasumi, M., Kaneko, H., & Ishiguro, N. (2009) · Journal of Pediatric Orthopaedics · doi:10.1097/bpo.0b013e3181b2afb2 · Cited by 49 · see citing works
Trombi, L., Mattii, L., Pacini, S., D’Alessandro, D., Battolla, B., Orciuolo, E., Buda, G., Fazzi, R., Galimberti, S., & Petrini, M. (2007) · Journal of Orthopaedic Research® · doi:10.1002/jor.20490 · Cited by 41 · see citing works
Self-citationXiang, Y., Zheng, Q., Jia, B., Huang, G., Xu, Y., Wang, J., & Pan, Z. (2007) · Journal of Zhejiang University SCIENCE B · doi:10.1631/jzus.2007.b0136 · Cited by 37 · see citing works
Biomolecular strategies of bone augmentation in spinal surgery
Pneumaticos, S. G., Triantafyllopoulos, G. K., Chatziioannou, S., Basdra, E. K., & Papavassiliou, A. G. (2011) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2010.12.002 · Cited by 31 · see citing works
Selective Culture of Mesodermal Progenitor Cells
Trombi, L., Pacini, S., Montali, M., Fazzi, R., Chiellini, E., Ikehara, S., & Petrini, M. (2009) · Stem Cells and Development · doi:10.1089/scd.2009.0054 · Cited by 30 · see citing works
Self-citationAn autologous fibrinogen‐based adhesive for use in otologic surgery
Silberstein, L. E., Williams, L., Hughlett, M. A., Magee, D. A., & Weisman, R. A. (1988) · Transfusion · doi:10.1046/j.1537-2995.1988.28488265257.x · Cited by 30 · see citing works
Trombi, L., D’Alessandro, D., Pacini, S., Fiorentino, B., Scarpellini, M., Fazzi, R., Galimberti, S., Guazzini, S., & Petrini, M. (2008) · Transfusion · doi:10.1111/j.1537-2995.2008.01829.x · Cited by 23 · see citing works
Self-citationPersistent Iliac Crest Donor Site Pain: Independent Outcome Assessment
Heary, R. F. (2002) · Neurosurgery · doi:10.1097/00006123-200209000-00061 · Cited by 21 · see citing works
Effect of bone graft substitute on marrow stromal cell proliferation and differentiation
Siggers, K., Frei, H., Fernlund, G., & Rossi, F. M. V. (2010) · Journal of Biomedical Materials Research Part A · doi:10.1002/jbm.a.32766 · Cited by 17 · see citing works
Vulcano, E., Murena, L., Cherubino, P., Falvo, D. A., Rossi, A., Baj, A., & Toniolo, A. (2012) · PubMed · Cited by 11 · see citing works
Charles, M., Barr, T., Clokie, C. M. L., & Sándor, G. K. B. (2007) · PubMed · Cited by 9 · see citing works
The treatment of pseudarthrosis using the Ilizarov method.
Niedzielski, K. R., & Synder, M. A. (2000) · PubMed · Cited by 4 · see citing works
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Strangis, G., Labardi, M., Gallone, G., Milazzo, M., Capaccioli, S., Forlì, F., Cinelli, P., Berrettini, S., Seggiani, M., Danti, S., et al. (2024) · Bioengineering · doi:10.3390/bioengineering11020193 · Cited by 32 · see citing works
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Lana, J. F., da Fonseca, L. F., Azzini, G. O. M., Santos, G. S., Braga, M., Cardoso, A. M., Murrell, W., Gobbi, A. W., Purita, J. R., & de Andrade, M. A. P. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22052762 · Cited by 31 · see citing works
Al-Delfi, I. R. T., Sheard, J., Wood, C. R., Vernallis, A. B., Innes, J., Myint, P., & Johnson, W. E. B. (2016) · The Veterinary Journal · doi:10.1016/j.tvjl.2016.09.003 · Cited by 19 · see citing works
Baron, M., Drohat, P., Crawford, B., Hornicek, F. J., Best, T. M., & Kouroupis, D. (2023) · Bioengineering · doi:10.3390/bioengineering10101187 · Cited by 19 · see citing works
Savelli, S., Trombi, L., D’Alessandro, D., Moscato, S., Pacini, S., Giannotti, S., Lapi, S., Scatena, F., & Petrini, M. (2018) · Cytotherapy · doi:10.1016/j.jcyt.2017.12.013 · Cited by 16 · see citing works
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Sauer, T., Facchinetti, G., Kohl, M., Kowal, J. M., Rozanova, S., Horn, J., Schmal, H., Kwee, I., Schulz, A., Hartwig, S., et al. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23052568 · Cited by 14 · see citing works
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- Authors
- Giannotti, S., Trombi, L., Bottai, V., Ghilardi, M., D'Alessandro, D., Danti, S., Dell'Osso, G., Guido, G., & Petrini, M.
- Affiliations
- University of Pisa (IT)
- Corresponding author
- Trombi, Luisa
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2013-11-12
- Volume
- 8
- Issue
- 11
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3825750
- OpenAlex
- W4236603982
- Cited by
- 12
- References
- 51
- Citations by year
- 2026: 1 · 2024: 1 · 2023: 1 · 2022: 1 · 2021: 2 · 2020: 1 · 2019: 1 · 2018: 2 · 2016: 2
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- CINECA IRIS Institutial research information system (University of Pisa) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Health Sciences › Medicine › Epidemiology › Bone fractures and treatments
- Physical Sciences › Engineering › Biomedical Engineering › Bone Tissue Engineering Materials
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Keywords
- nonunion, upper limb, mesenchymal stem cells, tissue engineering, bone marrow-derived MSCs, osteogenic differentiation, ex vivo cell expansion, bone grafting, long-term safety, bone regeneration
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