Branko Skovrlj1, Javier Z Guzman2, Motasem Al Maaieh2, Samuel K Cho2, James C Iatridis2, Sheeraz A Qureshi3. 1. Department of Neurosurgery, Icahn School of Medicine at Mount Sinai, 1 Gustave L Levy Place, Box 1136, New York, NY 10029, USA. 2. Department of Orthopaedics, Icahn School of Medicine at Mount Sinai, 5 East 98th St, 9th Floor, Box 1188, New York, NY 10029, USA. 3. Department of Orthopaedics, Icahn School of Medicine at Mount Sinai, 5 East 98th St, 9th Floor, Box 1188, New York, NY 10029, USA. Electronic address: sheerazqureshi@mountsinai.org.
Abstract
BACKGROUND CONTEXT: Advances in the field of stem cell technology have stimulated the development and increased use of allogenic bone grafts containing live mesenchymal stem cells (MSCs), also known as cellular bone matrices (CBMs). It is estimated that CBMs comprise greater than 17% of all bone grafts and bone graft substitutes used. PURPOSE: To critically evaluate CBMs, specifically their technical specifications, existing published data supporting their use, US Food and Drug Administration (FDA) regulation, cost, potential pitfalls, and other aspects pertaining to their use. STUDY DESIGN: Areview of literature. METHODS: A series of Ovid, Medline, and Pubmed-National Library of Medicine/National Institutes of Health (www.ncbi.nlm.nih.gov) searches were performed. Only articles in English journals or published with English language translations were included. Level of evidence of the selected articles was assessed. Specific technical information on each CBM was obtained by direct communication from the companies marketing the individual products. RESULTS: Five different CBMs are currently available for use in spinal fusion surgery. There is a wide variation between the products with regard to the average donor age at harvest, total cellular concentration, percentage of MSCs, shelf life, and cell viability after defrosting. Three retrospective studies evaluating CBMs and fusion have shown fusion rates ranging from 90.2% to 92.3%, and multiple industry-sponsored trials are underway. No independent studies evaluating spinal fusion rates with the use of CBMs exist. All the commercially available CBMs claim to meet the FDA criteria under Section 361, 21 CFR Part 1271, and are not undergoing FDA premarket review. The CBMs claim to provide viable MSCs and are offered at a premium cost. Numerous challenges exist in regard to MSCs' survival, function, osteoblastic potential, and cytokine production once implanted into the intended host. CONCLUSIONS: Cellular bone matrices may be a promising bone augmentation technology in spinal fusion surgery. Although CBMs appear to be safe for use as bone graft substitutes, their efficacy in spinal fusion surgery remains highly inconclusive. Large, nonindustry sponsored studies evaluating the efficacy of CBMs are required. Without results from such studies, surgeons must be made aware of the potential pitfalls of CBMs in spinal fusion surgery. With the currently available data, there is insufficient evidence to support the use of CBMs as bone graft substitutes in spinal fusion surgery.
BACKGROUND CONTEXT: Advances in the field of stem cell technology have stimulated the development and increased use of allogenic bone grafts containing live mesenchymal stem cells (MSCs), also known as cellular bone matrices (CBMs). It is estimated that CBMs comprise greater than 17% of all bone grafts and bone graft substitutes used. PURPOSE: To critically evaluate CBMs, specifically their technical specifications, existing published data supporting their use, US Food and Drug Administration (FDA) regulation, cost, potential pitfalls, and other aspects pertaining to their use. STUDY DESIGN: Areview of literature. METHODS: A series of Ovid, Medline, and Pubmed-National Library of Medicine/National Institutes of Health (www.ncbi.nlm.nih.gov) searches were performed. Only articles in English journals or published with English language translations were included. Level of evidence of the selected articles was assessed. Specific technical information on each CBM was obtained by direct communication from the companies marketing the individual products. RESULTS: Five different CBMs are currently available for use in spinal fusion surgery. There is a wide variation between the products with regard to the average donor age at harvest, total cellular concentration, percentage of MSCs, shelf life, and cell viability after defrosting. Three retrospective studies evaluating CBMs and fusion have shown fusion rates ranging from 90.2% to 92.3%, and multiple industry-sponsored trials are underway. No independent studies evaluating spinal fusion rates with the use of CBMs exist. All the commercially available CBMs claim to meet the FDA criteria under Section 361, 21 CFR Part 1271, and are not undergoing FDA premarket review. The CBMs claim to provide viable MSCs and are offered at a premium cost. Numerous challenges exist in regard to MSCs' survival, function, osteoblastic potential, and cytokine production once implanted into the intended host. CONCLUSIONS: Cellular bone matrices may be a promising bone augmentation technology in spinal fusion surgery. Although CBMs appear to be safe for use as bone graft substitutes, their efficacy in spinal fusion surgery remains highly inconclusive. Large, nonindustry sponsored studies evaluating the efficacy of CBMs are required. Without results from such studies, surgeons must be made aware of the potential pitfalls of CBMs in spinal fusion surgery. With the currently available data, there is insufficient evidence to support the use of CBMs as bone graft substitutes in spinal fusion surgery.
Authors: Brian Johnstone; Nianli Zhang; Erik I Waldorff; Eric Semler; Anouska Dasgupta; Marcel Betsch; Paolo Punsalan; Holly Cho; James T Ryaby; Jung Yoo Journal: Int J Spine Surg Date: 2020-04-30
Authors: Rodolfo E De la Vega; Aysegul Atasoy-Zeybek; Joseph A Panos; Martijn VAN Griensven; Christopher H Evans; Elizabeth R Balmayor Journal: Transl Res Date: 2021-05-05 Impact factor: 10.171
Authors: Cliff Lin; Nianli Zhang; Erik I Waldorff; Paolo Punsalan; David Wang; Eric Semler; James T Ryaby; Jung Yoo; Brian Johnstone Journal: JOR Spine Date: 2020-03-15
Authors: Patrick C Hsieh; Zorica Buser; Andrea C Skelly; Erika D Brodt; Darrel Brodke; Hans-Joerg Meisel; Jong-Beom Park; S Tim Yoon; Jeffrey C Wang Journal: Global Spine J Date: 2019-05-08