What is Needed for Optimal Fusion? Celeste Abjornson, Ph.D. Director of the Integrated Spine Research Program Hospital for Special Surgery
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1 What is Needed fr Optimal Fusin? Celeste Abjrnsn, Ph.D. Directr f the Integrated Spine Research Prgram Hspital fr Special Surgery Bne Healing: A Symphny f Events 2 Chemtaxis (attracts cells) Stem Cell Elabratin f Matrix TGF- PDGF BMPs IGFs FGFs BMPs GDFs BMPs PDGF, TGF-, IGFs and Angigenesis Orchestrated Bne Healing Differentiatin Cmmitment Prliferatin Prgressin VEGF, EGF Grwth Factrs: PDGF, TGF- IGFs, FGFs Remdeling Maturatin Cmmitted Bne Cell (presteblast) Functinal Tissue BMPs, Hrmnes, GFs released during remdeling
2 Bilgics Buffet Synthetics DBM BMP Stem Cells Autgraft/ Allgraft PRP 5/27/206 4 What is the ideal graft? A cmpsite f the right cmpnents Cells + Matrix + Signals Hst r Cultured Structure r Vid Filler DBM r Grwth Factr 5 January 0, 2002 Infuse Panel The Hly Grail Wuld revlutinize spine surgery Slve the previusly unslvable 2
3 Bne Mrphgenetic Prtein 8 BMP Cervical Spine Edema Ostelysis Serma 9 3
4 YODA Studies 0 What alternatives d we have? Allgraft-based Cancellus Crtical DBM Synthetic Calcium Cllagen Hydrxyapatite PEEK 5/27/206 Stem cells Grwth factrs BMP Graft Optin: Ostegenic Agents PRP Systems Spin whle venus bld fr buffy cat which cntains platelets, etc. Bne Marrw Aspirate cntains real bne frming cells Idea is t get enugh PDGF t help bne frmatin Studies in Eurpe shw exact ppsite suspecting high levels f TGF- prven t frm bne physilgically relevant amunts f all factrs the true ccktail f factrs 2 4
5 MSCs / Marrw Cells 0,000 00,000 Estimates btained by CFU-F assay 250, ,000 2,000,000 Age (years) Based n A Caplan 2007 J Cell Physil Imprtant PRP papers Carren et al. clinical retrspective cmparing ICBG vs. ICBG + PRP in psterlateral lumbar fusin 76 patients received -level (74%), 2-level (20%) r 3-level (6%) ICBG + PRP 76 age cntrl match 2 years, 25% nn-unin ICBG + PRP vs. 7% nn-unin ICBG (nt stat sig) Weiner et al. clinical retrspective cmparing ICBGvs. ICBG + PRP in psterlateral lumbar fusin 9% fusin with ICBG vs. 62% fusin with ICBG + PRP 4 Why are PRP systems nt wrking??? Platelet gels may disslve relatively rapidly thrugh fibrinlysis The grwth factrs in platelet gels may be t lw t have any stegenic effect Pssible presence f grwth factrs that inhibit bne frmatin Platelets might nt survive centrifuge techniques Huge difference between systems 5 5
6 Platelet Rich Fibrin Membrane 6 PRFM: Prvides Sustained Release f Grwth Factrs Sustained grwth factr release ver time (7+ Days) t replicate the nrmal healing prcess 3 Carrll RJ, Arnczky SP, O Cnnell SM Stem Cell Therapies Cell-based therapy Autlgus Allgeneic Weaker stimulus Mre clinically applicable Pint-f-care techniques Questins? Which tissue? What kind f cells? Hw many cells? Hw prcessed? Which carrier? 8 6
7 Hmlgus Use 2 CFR 27.3(c): Hmlgus use means the repair, recnstructin, replacement, r supplementatin f a recipient s cells r tissues with an HCT/P (Human Cellular r Tissue Prduct) that perfrms the same basic functin r functins in the recipient as in the dnr. Essentially, the HCT/P must be used in a manner similar t its natural endgenus functin r it is termed a Bilgical Drug. 20 Embrynic/Amnitic Amnitic Fluid Derived Stem cells Amnitic derived fluid cntains varius grwth factrs and amnitic stem cells Cllected frm live dnrs Cncerns: Number f cells is unknwn hafsc (Amnitic Fluid Stem Cells) Which tissue did they cme frm? Cell viability testing- Unknwn Same cntrversy as embrynic stem cells Nt allwed in all health systems Nt Hmlgus Use 7
8 What is a Stem Cell Allgraft? Crypreserved allgraft bne matrix that cntains viable bne frming cells and demineralized bne matrix HCT/P Autgraft substitute with reliable number f living cells and steinductive ptential Pssesses necessary healing cmpnents Ostegenic: cntains MSCs and OPCs Osteinductive : DBM cmpnent & MSCs Ostecnductive: cancellus bne cmpnent 22 Cells Are Alive After Crypreservatin & Thawing f Stem Cell Allgraft Viable cells cnfirmed after prcessing using live/dead staining 23 Stem Cell Allgrafts D Nt Elicit an Immune Respnse Cancellus bne prir t prcessing HSCs depleted and stegenic cells remaining after prcessing Cells are immunpriviledged Cells d nt stimulate immune respnse: they lack MHC/HLA class II antigens (Majr Histcmpatibility cmplex: MHC/Human Leukcyte antigen: HLA) MSCs als secrete cytkines that mdulate immune reactins 24 8
9 What is Needed t Optimize Fusin??? Supprt r enhance repair accrding t the functinal needs f the site Bicmpatiable Replaced by hst bne Tailred t the prcedure 25 just because yu use it in the gutters desn t make it a gd chice fr yur interbdy Spacer w/ DBM (Minimal Endplate Cntact) Spacer w/ Spnge (Intimate Endplate Cntact) 26 Title f Presentatin Here Thank Yu 27 9
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