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7Volume 6, Issue 14 MAY 4, 2010The study looked at patients whowere treated at Centeno’s clinic fora variety of orthopedic conditionsusing his Regenexx culture-expanded,autologous, bone marrow-derivedMSCs. As described in his paper,the cells were cultured in monolayerculture flasks using an autologousplatelet lysate technique and then reinjected into the subject’s peripheraljoints or intervertebral discs. Followup MRIs over the course of two yearsfailed to demonstrate any tumorformation at the re-implant sites.That is, incidentally, consistent withother research which has found noevidence of malignant cellular changedue to and after implantation ofexpanded MSCs.Another paper, a review, waspublished in Medical Hypotheses, inSeptember 2008 titled “Regenerationof meniscus cartilage in a knee treatedwith percutaneously implantedautologous mesenchymal stem cells”.The paper, which was authored by Dr.Centeno, presents his experience usinghis techniques with autologous MSCtherapy and, no surprise, reports thatit was a “successful harvest, expansion,and transplant of autologousmesenchymal stem cells into anadult human knee that resulted in anincrease in meniscal cartilage volume.”local surgeons to inject cells after kneemicro fracture procedures.”RSI charges between 7,000- 8,500for the treatment—depending onindication. This price includes themarrow and blood draw, lab expansionof the cells, pre-injection, re-injectionof cells, and post injection(s). Theprocedure is not covered by insurance,something Centeno hopes will changesoon. “There are about 11,000published articles on autologousmesenchymal stem, so yes, with thattype of publishing activity (severalthousand papers a year), it’s likely tobe a foregone conclusion that atsome point, in my opinion, thistype of stem cell therapy will getinsurance approval.”The FDA ConundrumWalter Gardner, Chief of theConsumer Affairs Branch at theCenter for Biologics Evaluation andResearch at FDA says “Currently thereare no autologous stem cell therapieslicensed for use in the United States.Stem cells are regulated by Center forBiologics Evaluation and Research(CBER) as human cells, tissues andcellular and tissue-based products(HCT/Ps). Under the authority ofSection 361 of the Public HealthService (PHS) Act, FDA establishedregulations for all HCT/Ps to preventthe transmission of communicabledisease.” Under these well establishedand carefully monitored rules,tissues based products must be usedonly for homologous purposes andduring processing be “minimallymanipulated”. Culturing is notminimal manipulation according tothe FDA.“The Regenexx procedure is needlebased, so it’s less invasive thantraditional surgery,” says Centeno.“There is also opportunity toprovide MSCs with traditional orminimally invasive orthopedicsurgery techniques. MSCs have beenshown to aid in cartilage, meniscus,ligament, tendon, and bone healing.In addition, they also seem toimprove osteointegration of grafts.For example, we have worked withThere are a fair number of stemcell based products working theirway through the FDA clinical studyprocess in order to demonstrate to aTable 1. Cartilage Volume Analysis in mm3 from the case report: Increased knee cartilage volume in degenerative joint diseaseusing percutaneously implanted, autologous mesenchymal stem cells, platelet lysate and dexamethasoneImagePre-Injection6 MonthsArea of MeasurementCartilage SurfaceMeniscusDefectCartilage SurfaceMeniscusDefectVolume (N 35.11.1566.957.510.8887.1120.290.67% Change fromPre-Injection-0.490.78-28.99Source: RSI1-877-817-6450 www.ryortho.com

8Volume 6, Issue 14 MAY 4, 2010two-year research study thatwent through IRB approval[Institutional Review Board].We asked regulatory counselif we needed FDA approvaland received the opinionthat we didn’t require thatapproval since there wasno intent to make this aproduct, just simply usethis procedure as partof our medical practicein Colorado.”advertisementstatistically significant degree that theyare safe and efficacious. Most of theseproducts are based on cultured stemcells. But not all. Some are based onautologous products and others arebased on systems that allow physiciansto harvest the patient’s own stem cells.It would appear that RSI’s approachis either in a gray area or fits into onecorner of the regulations where, solong as the cultured MSCs are usedin the clinic and for its own patientsand not sold to other clinics, they areinside the bounds of the law.Then there is the fact that these areautologous materials. Autologousstem cell therapies use a patient’s ownbone marrow, blood, adipose tissuesor even tooth enamel to collect MSCs.According to Dr. Centeno, usingautologous source material brings therisk of disease transmission tovirtually zero.Said Dr. Centeno, “We began thisprocedure in 2005 as part of a biggerHe cites the example ofa surgeon in his garageformulating a new surgicalinstrument, which he thensterilizes and uses in surgerythe next day. Since the FDAonly regulates drugs and devices soldin interstate commerce, Centeno saysthat surgeon is under no obligationto seek FDA approval for his customsurgical instrument. “However, if thatsurgeon started taking orders fromother surgeons around the countryfor that device and began shippingdevices ‘interstate’, he would thenrequire FDA approval on the device.”He says the same holds true for stemcells. FDA approval he adds, wouldonly be needed if donor stem cellswere shipped in a vial “interstate.”that point the doctors filed a lawsuitbut a ruling came down stating that“we couldn’t file against them untilthey did something. We filed a noticeof appeal and asked to have a courtenforced mediation started,”says Centeno.For their part, Drs. Centeno andSchultz now sit on the Board ofDirectors of the InternationalCellular Medicine Society and haveestablished a three-point processwhich takes a note from the IVF (invitro fertilization) community tocreate safety guidelines for physiciansinterested in offering this therapy.“The fertility specialists have formedprofessional organizations that haveestablished professional guidelines,lab guidelines with third party audits,and a re-implantation registry. We’vedone the same. We have workedwith physicians and scientists toestablish professional guidelines forsafe autologous stem cell use, labguidelines with a third party auditor(Reglera), and a third party non-profitre-implantation registry. There are nowabout 250 physicians and scientiststhat have joined this organization.”Centeno says that upon receivingan “untitled letter” from the FDAquestioning parts of their practice, theclinic responded and in the summerof 2009, “They visited our Coloradosite,” explains Centeno “and declaredthat since we were culturing cells, wewere manufacturing a biologic drug.We again asked for them to supporttheir position that they had regulatoryauthority with some logical argument,again they declined to comment.” At1-877-817-6450 www.ryortho.com

9Volume 6, Issue 14 MAY 4, 2010The Soldier in the Pink DressBy Robin YoungHer name is Crystal. The dresswas certainly pink and itshowed plenty of Crystal’sshoulder, back and front. Crystal wasstanding among a small group of awardwinners for the American Academy ofOrthopaedic Surgeons (AAOS) banquetthis past week in Washington. D.C.Amidst the blue, gray, and black suitsand evening gowns, Crystal was acolorful exotic flower.was the subject of a documentary thatwas a MORE award winner for 2009.She’s an amputee.and producer to come to podium,Crystal came too. She also said afew words.All of the MORE award winners sit inthe front row of a large room and thenwalk up to a podium when called. JohnJ. Callaghan, M.D., President of AAOSthis year, did the honors. The film,Fighting for Life, was the last MOREaward winner to be called. TerrySanders (co-producer and two-timeAcademy Award winning film maker),Tammy Alvarez (executive producer),Sgt Abdul Madjid, USMC, one of thesubjects of the film and SPC CrystalDavis, U.S. Army, the other subject ofthe film, came to the podium.Paraphrasing her, she said: “I wantto thank the filmmakers for helpingme through my recovery. I wanted todo my best in front of the camera sohaving them there motivated me. Isaid to myself, if I can work hard infront of the camera, I can work hardbehind the camera too. So I did.”Crystal also thanked her father andother family members and then sheended with a joke. “So, thank you tothe doctors and the filmmakers forhelping me to get a leg up.”The film documents today’s militarysurgeons as they go through trainingand then deployment. It also followstwo casualties of our wars in Iraq andAfghanistan as they are treated bythese military surgeons and nurses. Inthe film we meet Crystal Davis as sheis being medivaced. Her surgeon istelling her that he had to amputate herleft leg and her right leg was iffy. She’snegotiating hard to keep the right leg.SPC Crystal Davis/Courtesy of AAOS.orgShe also had large tattoos on bothshoulders, back and, yes, over theswell of her bosom.It was hard not to notice Crystal.Lauren Pearson, AAOS’s Manager ofMedia Relations told me that CrystalSPC Crystal Davis is an Army truckdriver. Every other truck passed overthat particular stretch of gravel in Iraqin 2008 but when Crystal’s truck wentover, the hidden IED detonated.Like all great art, this film capturesthe powerful emotional journey thatCrystal, her family, and her caregiverswent through. There were very fewdry eyes in the audience this pastWednesday night. Even Crystal’s.When the time came for the filmmakerThe standing ovation lasted about10 minutes.The intersection of art, war, andorthopedics can be unexpectedlyaffecting. In addition to this particularfilm—which is available from theAmerican Film Foundation (contact:krisbubna@hotmail.com ) and westrongly, highly, urgently suggest thatyour hospital or community groupor church rent a copy of this film andshow it—there is an exhibition andbook of such art that is also available.Sandy Gordon, AAOS’s PublicRelations Director, organized boththe MORE Award and the exhibit ofwar time art as created by surgeonsand nurses! To learn more about theAAOS Wounded in Action art exhibit,please visit the Web site: http://www.woundedinactionart.org/ or contactSandy Gordon, AAOS PublicRelations Director, at 847 384-4030or gordon@aaos.org.1-877-817-6450 www.ryortho.com

10Volume 6, Issue 14 MAY 4, 2010Here are five (of 103) works that are part of this great, great exhibition.Home from the War by Joseph A. Pearson(36 x 25 in. Oil on Canvas)Pearson, whose mother lost both legs to diabetes,was inspired to paint this image after seeing a youngveteran, an amputee, in a coffee shop. It shows a doubleamputee strapping on an artificial leg. “I was moved bythe sacrifice he’d made for America,” he says. Joseph A.Pearson, a New Orleans, Louisiana-based artist, servedas an illustrator in the U.S. Army from 1976 to 1979.He started drawing at age 5, inspired by the illustrationshe saw in a Sears, Roebuck & Co. catalog. At the time,he was fascinated by “the magic of making a figure outof lines and shade.” His artwork now includes portraits,murals, and human figures, but drawing figures remainshis passion. “My strength as an artist lies in my passionfor the familiar faces, figures, and scenes of the loving,but ordinary facets of life: the human condition. Mygoal is to translate this condition into a universal pointof view. My impetus begins with the human spirit andthe desire to witness the love that spirit brings into theworld,” Pearson says.Wounded Warrior by Richard McCarthy M.D.(20 x 30 x .5 in. Acrylic on Canvas)Dr. McCarthy’s eldest son, Bryan, who spent eight monthspiloting an F-18 Super Hornet in Afghanistan, inspired himto paint this picture. “His audacious confidence in the abilityof the Navy to bring him back home safely caused me toreflect and paint this image of determination and frailty,” hesays. It shows a veteran, who lost his left arm to an explosivedevice, in front of an American flag. As a medical student,Dr. Richard E. McCarthy visited his sister, a Navy nurse, asshe cared for returning Vietnam veterans at the now-defunctPhiladelphia Naval Hospital. This early exposure to woundedsoldiers made a lasting impression on him. “I was struckwith the stark reality of missing parts in these young warriorstrying to piece their lives together,” says Dr. McCarthy, whowas 21 at the time. More recently, the graduation of hisyoungest son, Andrew, from the United States Naval Academyin Annapolis, Maryland, renewed his respect and admirationfor the men and women of the uniformed services.1-877-817-6450 www.ryortho.com

11Volume 6, Issue 14 MAY 4, 2010Naval Officer/Amputee 1973by Peter Langan, M.D.(24 x 48 in. Oil on Canvas)Dr. Langan starting painting after a knee injury. This canvasshows a lieutenant commander, who has lost a leg, walkingon crutches in his dress blues uniform. Dr. Peter Langan, aMineola, New York-based orthopedic surgeon, served in theU.S. Navy with the 2nd Marine Division from 1971 to 1973,an experience that is still fresh in his mind more than 30years later. He is well aware of the personal and professionalsacrifices made by soldiers. When treating injured troops, “Itry to reciprocate,” he says. Dr. Langan believes that researchplays a big role in orthopedic advancements, such as thedevelopment of rods and plates to stabilize fractures. But themost fundamental change has been the speed with which thewounded obtain care. “The military has done a great job ingetting the hospital to the injured,” he says.Patience by John Ton(44 x 20 in. Mixed Media: Spent Ammunition Cases)This image, made of spent ammunition cases, depicts the “chronicpatience required by a physically disabled person,” Ton says. It is hishope that those who view it will reflect on this patience, and gain somepatience for themselves. “Regardless of where people stand politicallyon the gun issue, I want them to first see the beauty of the textures andpatinas of the material I have chosen,” he says. As a self-taught artist,John Ton has created his own mixed media technique, by using spentammunition casings to produce art. “There is a mountain I often hikeon near Reno, where I live, that is littered with shotgun shell cases.My first thoughts were that this unsightly litter might somehow berecycled; it then occurred to me that perhaps some form of art mightbe made from them. They have an apparently infinite variety of colors,and the casings that have weathered in the sun for a while can fadeto a very interesting light blue, lavender, and even white sometimes,”Ton says. He now collects bullet shells from public and “unsanctioned”ranges in Nevada and California and uses them to make “ammosaics,”with images reflecting the realities of accident victims, including thosehe meets as a volunteer at the V.A. Sierra Nevada Health Care System inReno, Nevada.1-877-817-6450 www.ryortho.com

12Volume 6, Issue 14 MAY 4, 2010Concern by COL Colin Miller, MD(8 x 11 in. Photograph)Dr. Miller’s first photo, from Afghanistan,captures the trauma on a young girl’s faceas her wrist injury is examined and herfather looks on. When casualties increasedat Ibn Sina Hospital in Baghdad, Col.Colin K. Miller, M.D., had little time forhis passion—photography. Orthopedicsurgeons at Baghdad E.R., as it ispopularly known, had to work aroundthe clock to operate on injured soldiers,snatching catnaps when they could.Instead, Dr. Miller resorted to takingphotos in his “downtime”—out of an openBlackhawk helicopter window en routeto Baghdad International Airport or whilewaiting in a bunker for a siren to stop.His images immortalize intense momentsfrom his experiences in combatmedicine—experiences that have madehim a better surgeon, leader, and person.“I can’t imagine a better job than caring forwounded soldiers,” he says.Again, don’t hesitate to contact AAOS for acopy of this powerful exhibit’s book and dofind a way to show the movie, Fighting for Lifein your hospital, church or other organization.advertisement1-877-817-6450 www.ryortho.com

13Volume 6, Issue 14 MAY 4, 2010NuVasive Sues Orthofix Over Stem CellsBy Walter Eisneragainst Orthofix for allegedlyinfringing the ‘239 patentbehind NuVasive’s OsteocelPlus biologic product. NuVasivepurchased the licensng rights tothat patent from Osiris for 85million in 2008.Orthofix: Suit WhollyWithout MeritOrthofix’s CEO, Alan Milinazzowas unaware of the action, notyet having been served withpapers and issued this statementthe following day.“At best, we find both theNuVasive announcementand the forum for theannouncement questionable.We prefer to compete inthe marketplace so that wecan continue to bring nextgeneration technologies tothe market for the benefit ofpatients and surgeons who treatthem. It is Orthofix’s policy torespect the intellectual propertyrights of others, and weare prepared to vigorouslydefend ourselvesagainst any allegations tothe contrary.”RRY Publications LLCDuringNuVasive’squarterlyconference call withanalysts on April 20,company Chairmanand CEO AlexisLukianov dropped, ifnot a bombshell, atleast a stink bomb.He told analyststowards the end ofthe call that NuVasivehas begun legal actionDuring his own conferencecall with Wall Streetanalysts on April 28,Milinazzo told analyststhat the suit was “whollywithout merit.”Alex LukianovHe told analysts that priorto developing its ownproduct, TrinityEvolution, thecompany did its duediligence and founda, “novel nextgeneration” productand did not infringeon the intellectualAlan Milinazzoproperty licensed byNuVasive.Biologic IP in orthopedics is a big dealand this lawsuit encapsulates business,scientific and legal issues that have yetto be decided in courts and markets.With a stroke of the pen, AlexisLukianov and NuVasive have sentthese issues to a federal court. Theworld of orthopedics may be about"GUFS IJT TUBUF PG UIF BSU PSUIPQFEJD TVSHFSZ JN 4UFWFOT DPVME TLJ B CMBDL EJBNPOE 5IFSFµT OPU B DIBODF IF XJMM CVU IF DPVME Getting people back to their real lives.That’s what we at Fort Wayne Metals,makers of high grade medical wire, do best.advertisementFWM Ortho ThsWk.indd 11/26/09 9:54:50 AM1-877-817-6450 www.ryortho.com

14to learn a lot about the legal nature ofstem cell patents for use in promotingbone growth.NuVasive/Osiris v Orthofix/MTFIn a nutshell NuVasive is saying thatOsiris spent lots of time and moneyto learn that allogeneic mesenchymalstem cells (MSCs) can be harvestedfrom a donor, dead or alive, and givento a patient without fear of rejection topromote bone growth.Until this important breakthrough ofthe ‘239 patent, it was widely believedthat allogeneic cells posed a risk ofbeing a foreign cell surface proteinthat would trigger an adverse immuneresponse in the patient receiving thecells. NuVasive says the inventors ofthe patent, “put those fears to rest.”Osiris began exploring ways todevelop therapies and productsrelated to MSCs in the mid 90s andfiled for a patent.Volume 6, Issue 14 MAY 4, 2010Allogeneic MesenchymalStem CellsThe patent (No. 6,355,239), “Uses forNon-Autologous Mesenchymal StemCells,” was issued on March 12, 2002,to the inventors, Scott Bruder, KevinMcIntosh, M.D., Daniel Marshak,M.D. and Joseph Mosca, M.D. andassigned to Osiris.According to NuVasive, the ’239Patent, “claims, inter alia, methodsfor treating a human subjectwith allogeneic MSCs to promoteconnective tissue (e.g., cartilage orbone) growth.”The suit claims the patent inventors,“surprisingly discovered thatallogeneic MSCs do not provoke anadverse immunological response bythe patient. The inventors’ teachingthat allogeneic MSCs can be usedin this fashion marked a significantadvancement in the art.”LaunchingCommercial ProductOsiris launched Osteocel in2005 as the first commercialproduct in the U.S. thatcontained adult allogeneicMSCs for use as a transplant.In 2006, Osiris went publicwith a valuation of 300million, the second-largestpublic stem cell company inthe U.S.advertisementIn March 2006, BlackstoneMedical made a deal withOsiris to distribute, nonexclusively, Osteocel foruse in promoting bone growth.Blackston

Nov 05, 2012 · Regenexx: Recipe for Controversy? The Centeno-Schultz Clinic’s Regenexx stem cell therapy is being marketed as a trea