Scientific Evidence



At iOrthoBIOLOGIXTM, we believe everything we do starting with in-depth comprehensive evaluation, our candidacy rating system, our customized treatment recommendations, and our advanced stem cell procedures themselves should be grounded in scientific evidence. As such we highlight just some of the current research available on the topic of Bio-Restorative & Stem Cell Orthopedics. There is no longer a scarcity of research and the mounting data is growing quickly.

iOrthoBIOLOGIX Regenerative Medicine Based Publications



Zeckser, J, Wolff, M, Tucker, J, Goodwin, J. “Multipotent Mesenchymal Stem Cell Treatment for Discogenic Low Back Pain and Disc Degeneration”. Stem Cells International. Volume 2016 (2016). Article ID 3908389, 13 pages

Jason Tucker, Christopher Centeno, and Jeff Ericksen. “Knee Osteoarthritis with Emphasis on Percutaneous Regenerative Medicine. Chapter 34. Case studies in Pain Management, ed. Alan David Kaye and Rinoo V. Shah. Published by Cambridge University Press. Volume 2015.

J.D Tucker, J.J. Ericksen, L.L.Goetz, L.W. Elmore. “Should clinical studies involving ‘Regenerative Injection Therapy,’ strive to incorporate a triad outcome measures instead of only including clinical outcome measures?” Osteoarthritis and Cartilage. June 2014. Volume 22, Issue 6. Pages 715-717.

Lauren Alexis Hoeferlin, Quoc K. Huynh, Jennifer A. Mietla, Scott A. Sell, Jason Tucker, Charles Edward Chalfant, and Dayanjan Shanaka Wijesinghe. “The lipid portion of activated platelet-rich plasma significantly contributes to its healing prosperities. Advances in Wound Care. Volume 4, Number 2. Feb 2015.



Non-iOrthoBIOLOGIX Publications: (includes human and animal studies)



General

Wyles, C, et al. Mesenchymal stem cell therapy for osteoarthritis: current perspectives. Stem Cells Cloning. 2015; 8: 117–124.

Caplan, A and D. Correa, “The MSC: an injury drugstore,” Cell Stem Cell, vol. 9, no. 1, pp. 11–15, 2011.

Friedenstein, A, I. I. Piatetzky-Shapiro, and K. V. Petrakova, “Osteogenesis in transplants of bone marrow cells,” Journal of Embryology and Experimental Morphology, vol. 16, no. 3, pp. 381–390, 1966.

Pittenger, M, A. M. Mackay, S. C. Beck et al., “Multilineage potential of adult human mesenchymal stem cells,” Science, vol. 284, no. 5411, pp. 143–147, 1999.

Petersen, B, ,W. C. Bowen, K. D. Patrene et al., “Bone marrow as a potential source of hepatic oval cells,” Science, vol. 284, no. 5417, pp. 1168–1170, 1999.

Kopen, G,D. J. Prockop, andD.G. Phinney, “Marrow stromal cells migrate throughout forebrain and cerebellum, and they differentiate into astrocytes after injection into neonatal mouse brains,” Proceedings of the National Academy of Sciences of the United States of America, vol. 96, no. 19, pp. 10711–10716, 1999.

Campagnoli, C, I. A. G. Roberts, S. Kumar, P. R. Bennett, I. Bellantuono, and N. M. Fisk, “Identification of mesenchymal stem/progenitor cells in human first-trimester fetal blood, liver, and bone marrow,” Blood, vol. 98, no. 8, pp. 2396–2402, 2001.

Karp, J andG. S. L. Teo, “Mesenchymal stem cell homing: the devil is in the details,” Cell Stem Cell, vol. 4, no. 3, pp. 206–216, 2009.

Uccelli, A, L. Moretta, and V. Pistoia, “Mesenchymal stem cells in health and disease,” Nature Reviews Immunology, vol. 8, no. 9, pp. 726–736, 2008.

Doorn, J, G. Moll, K. Le Blanc, C. van Blitterswijk, and J. de Boer, “Therapeutic applications of mesenchymal stromal cells: paracrine effects and potential improvements,” Tissue Engineering Part B: Reviews, vol. 18, no. 2, pp. 101–115, 2012.

Silva Meirelles, L A. M. Fontes, D. T. Covas, and A. I. Caplan, “Mechanisms involved in the therapeutic properties of mesenchymal stem cells,” Cytokine and Growth Factor Reviews, vol. 20, no. 5-6, pp. 419–427, 2009.

Manferdini, C. Adipose-Derived Mesenchymal Stem Cells Exert Antiinflammatory Effects on Chondrocytes and Synoviocytes from Osteoarthritis Patients Through Prostaglandin E2. Arthritis & Rheumatism. Vol. 65, No. 5, May 2013, pp 1271–1281

Schmitt, A, et al. Application of Stem Cells in Orthopedics. Stem Cells Int. 2012; 2012:

Tinsley, B, et al. Platelet-Rich Plasma Non-operative Injection Therapy—A Review of Indications and Evidence. Oper Tech Sports Med : 2012 20:192-200

Nguyen, R, et al. Applications of Platelet-Rich Plasma in Musculoskeletal and Sports Medicine: An Evidence-Based Approach. PM R 2011;3:226-250

Malanga, G. Regenerative Treatments for Orthopedic Conditions. PM R 7 (2015) S1-S3

Safety

Pak J, Chang JJ, Lee JH, Lee SH. Safety reporting on implantation of autologous adipose tissue-derived stem cells with platelet-rich plasma into human articular joints. National Center for Biotechnology Information. BMC Musculoskeletal Disord. 2013 Dec 1.

Centeno, C, et al. A multi-center analysis of adverse events among two thousand, three hundred and seventy two adult patients undergoing adult autologous stem cell therapy for orthopaedic conditions. International Orthopedics. Mar 2016. p. 1-11.

Hernigou P1, Homma Y2, Flouzat-Lachaniette CH1, Poignard A1, Chevallier N1, Rouard H1. Cancer risk is not increased in patients treated for orthopaedic diseases with autologous bone marrow cell concentrate. J Bone Joint Surg Am. 2013 Dec 18;95(24):2215-21.

Knee Pain

Agung M, Ochi M, Yanada S, Adachi N, Izuta Y, Yamasaki T, Toda K. “Mobilization of bone marrow-derived mesenchymal stem cells into the injured tissues after intraarticular injection and their contribution to tissue regeneration.” National Center for Biotechnology Information. Knee surgery, sports traumatology, arthroscopy : official journal of the ESSKA. 2006 Dec;14(12):1307-14. Epub 2006 Jun 20.

Cecilia Pascual-Garrido, A. Rolón, and A. Makino. “Treatment of Chronic Patellar Tendinopathy with Autologous Bone Marrow Stem Cells: A 5-Year-Followup.” National Center for Biotechnology Information. Stem Cells Int. 2012.

Vangsness CT Jr1, Farr J 2nd2, Boyd J3, Dellaero DT4, Mills CR5, LeRoux-Williams M5. Adult human mesenchymal stem cells delivered via intra-articular injection to the knee following partial medial meniscectomy: a randomized, double-blind, controlled study. J Bone Joint Surg Am. 2014 Jan 15;96(2):90-8.

Centeno, C, et al. Efficacy of autologous bone marrow concentrate for knee osteoarthritis with and without adipose graft. Biomed Res Int. 2014;2014:370621.

Centeno, C, J. R. Schultz, M. Cheever, B. Robinson, M. Freeman, andW.Marasco, “Safety and complications reporting on the re-implantation of culture-expanded mesenchymal stem cells using autologous platelet lysate technique,” Current Stem Cell Research andTherapy, vol. 5, no. 1, pp. 81–93, 2010.

Buda, R, F. Vannini,M. Cavallo, B. Grigolo, A. Cenacchi, and S. Giannini, “Osteochondral lesions of the knee: a new one-step repair technique with bone-marrow-derived cells,” Journal of Bone and Joint Surgery—Series A, vol. 92, no. 2, pp. 2–11, 2010.

Gobbi,A, G. Karnatzikos, C. Scotti, V. Mahajan, L. Mazzucco, and B. Grigolo, “One-step cartilage repair with bone marrow aspirate concentrated cells and collagen matrix in full-thickness knee cartilage lesions: results at 2-year follow-up,” Cartilage, vol. 2, no. 3, pp. 286–299, 2011.

Gobbi,A, G. Karnatzikos, and S. R. Sankineani, “One-step surgery with multipotent stem cells for the treatment of large full-thickness chondral defects of the knee,” The American Journal of Sports Medicine, vol. 42, no. 3, pp. 648–657, 2014.

Centeno, C, D. Busse, J. Kisiday, C. Keohan,M. Freeman, and D. Karli, “Increased knee cartilage volume in degenerative joint disease using percutaneously implanted, autologous mesenchymal stem cells,” Pain Physician, vol. 11, no. 3, pp. 343–353, 2008.

Centeno, C, D. Busse, J. Kisiday, C. Keohan,M. Freeman, and D. Karli, “Regeneration of meniscus cartilage in a knee treated with percutaneously implanted autologous mesenchymal stem cells,” Medical Hypotheses, vol. 71, no. 6, pp. 900–908, 2008.

Davatchi, F, B. S. Abdollahi, M. Mohyeddin, F. Shahram, and B. Nikbin, “Mesenchymal stemcell therapy for knee osteoarthritis. Preliminary report of four patients,” International Journal of Rheumatic Diseases, vol. 14, no. 2, pp. 211–215, 2011.

Emadedin, M, N. Aghdami, L. Taghiyar et al., “Intra-articular injection of autologous mesenchymal stem cells in six patients with knee osteoarthritis,” Archives of Iranian Medicine, vol. 15, no. 7, pp. 422–428, 2012.

Orozco,L, A.Munar, R. Soler et al., “Treatment of knee osteoarthritis with autologous mesenchymal stem cells: a pilot study,” Transplantation, vol. 95, no. 12, pp. 1535–1541, 2013.

Goyal, D, S. Keyhani, E. H. Lee, and J. H. P. Hui, “Evidence based status of microfracture technique: a systematic review of level I and II studies,” Arthroscopy, vol. 29, no. 9, pp. 1579–1588, 2013.

Saw, K, A. Anz, C. Siew-Yoke Jee et al., “Articular cartilage regeneration with autologous peripheral blood stem cells versus hyaluronic acid: a randomized controlled trial,” Arthroscopy, vol. 29, no. 4, pp. 684–694, 2013.

Saw,K, A. Anz, S. Merican et al., “Articular cartilage regeneration with autologous peripheral blood progenitor cells and hyaluronic acid after arthroscopic subchondral drilling: a report of 5 cases with histology,” Arthroscopy, vol. 27, no. 4, pp. 493– 506, 2011.

Wong,K, K. B. L. Lee, B. C. Tai, P. Law, E. H. Lee, and J. H. P.Hui, “Injectable cultured bone marrow-derived mesenchymal Stem cells in varus knees with cartilage defects undergoing high tibial osteotomy: a prospective, randomized controlled clinical trial with 2 years’ follow-up,” Arthroscopy—Journal of Arthroscopic and Related Surgery, vol. 29, no. 12, pp. 2020–2028, 2013.

Koh,Y, and Y.-J. Choi, “Infrapatellar fat pad-derived mesenchymal stem cell therapy for knee osteoarthritis,” Knee, vol. 19, no. 6, pp. 902–907, 2012.

Koh,Y, S.-B. Jo, O.-R. Kwon et al., “Mesenchymal stem cell injections improve symptoms of knee osteoarthritis,” Arthroscopy, vol. 29, no. 4, pp. 748–755, 2013.

Koh,Y, Y.-J. Choi, S.-K. Kwon, Y.-S. Kim, and J.-E. Yeo, “Clinical results and second-look arthroscopic findings after treatment with adipose-derived stem cells for knee osteoarthritis,” Knee Surgery, Sports Traumatology, Arthroscopy, 2013.

Jo,C, Y. G. Lee, W. H. Shin et al., “Intra-articular injection of mesenchymal stem cells for the treatment of osteoarthritis of the knee: a proof-of-concept clinical trial,” Stem Cells, vol. 32, no. 5, pp. 1254–1266, 2014.

Vangsness Jr., C, J. Farr, J. Boyd, D. T. Dellaero, C. R. Mills, and M. LeRoux-Williams, “Adult human mesenchymal stem cells delivered via intra-articular injection to the knee following partial medial meniscectomy,” The Journal of Bone and Joint Surgery A, vol. 96, no. 2, pp. 90–98, 2014.

Varma,H, B.Dadarya, and A. Vidyarthi, “The new avenues in The management of osteoarthritis of knee—stem cells,” Journal of the Indian Medical Association, vol. 108, no. 9, pp. 583–585, 2010.

Hauser,R, and A. Orlofsky, “Regenerative injection therapy with whole bone marrow aspirate for degenerative joint disease: a case series,” Clinical Medicine Insights: Arthritis and Musculoskeletal Disorders, vol. 6, pp. 65–72,

Koh, Y, S.-B. Jo, O.-R. Kwon et al., “Mesenchymal stem cell injections improve symptoms of knee osteoarthritis,” Arthroscopy, vol. 29, no. 4, pp. 748–755, 2013.

Koh, Y, Y.-J. Choi, S.-K. Kwon, Y.-S. Kim, and J.-E. Yeo, “Clinical results and second-look arthroscopic findings after treatment with adipose-derived stem cells for knee osteoarthritis,” Knee Surgery, Sports Traumatology, Arthroscopy, 2013.

Jo, C, Y. G. Lee, W. H. Shin et al., “Intra-articular injection of mesenchymal stem cells for the treatment of osteoarthritis of the knee: a proof-of-concept clinical trial,” Stem Cells, vol. 32, no. 5, pp. 1254–1266, 2014.

Vangsness Jr.,C, J. Farr, J. Boyd, D. T. Dellaero, C. R. Mills, and M. LeRoux-Williams, “Adult human mesenchymal stem cells delivered via intra-articular injection to the knee following partial medial meniscectomy,” The Journal

Vaquerizo V, etal. Comparison of Intra-Articular Injections of Plasma Rich in Growth Factors (PRGF-Endoret) Versus Durolane Hyaluronic Acid in the Treatment of Patients With Symptomatic Osteoarthritis: A Randomized Controlled Trial. Arthroscopy. 2013 Oct;29(10):1635-43.

Jang SJ, etal. Platelet-rich plasma (PRP) injections as an effective treatment for early osteoarthritis. Eur J Orthop Surg Traumatol. 2013 Jul;23(5):573-80.

Halpern B, etal. Clinical and MRI outcomes after platelet-rich plasma treatment for knee osteoarthritis. Sport Med. 2013 May;23(3):238-9.

Patel S, etal. Treatment with platelet-rich plasma is more effective than placebo for knee osteoarthritis: a prospective, double-blinded, randomized trial. Am J Sports Med. 2013 Feb;41(2):356-64.

Filardo, G. Platelet-rich plasma vs hyaluronic acid to treat knee degenerative pathology: study design and preliminary results of a randomized controlled trial. BMC Musculoskelet Disord. 2012 Nov 23;13:229. Say. Platelet-Rich Plasma Injection Is More Effective than Hyaluronic Acid in the Treatment of Knee Osteoarthritis. Acta Chir Orthop Traumatol Cech. 2013;80(4):278-283.

Shoulder Pain-Rotator Cuff

Hernigou P1, Flouzat Lachaniette CH, Delambre J, Zilber S, Duffiet P, Chevallier N, Rouard H. Biologic augmentation of rotator cuff repair with mesenchymal stem cells during arthroscopy improves healing and prevents further tears: a case-controlled study. Int Orthop. 2014 Sep;38(9):1811-8.

Gumucio JP, et al. Stromal vascular stem cell treatment decreases muscle fibrosis following chronic rotator cuff tear. Int Orthop. 2016 Apr;40(4):759-64.

Fickischerer, A, et al. Clinical management of rotator cuff tears. Current concepts in cell-based therapy strategies]. Orthopade. 2016 Feb;45(2):143-8

Tomero-Esteban, P, et al. Efficacy of supraspinatus tendon repair using mesenchymal stem cells along with a collagen I scaffold. J Orthop Surg Res. 2015 Aug 14;10:124

Valencia, M, et al. Stem cell therapy in the management of shoulder rotator cuff disorders. World J Stem Cells. 2015 May 26;7(4):691-9.

Spine (Low Back/Neck) Pain

Yetsa A. Tuakli-Wosornu, MD, MPH, Alon Terry, MD, Kwadwo Boachie-Adjei, BS, CPH, Julian R. Harrison, BS, Caitlin K. Gribbin, BA, Elizabeth E. LaSalle, BS, Joseph T. Nguyen, MPH, Jennifer L. Solomon, MD, Gregory E. Lutz, MD. “Lumbar Intradiskal Platelet-Rich Plasma (PRP) Injections: A Prospective, Double-Blind, Randomized Controlled Study.” American Academy of Physical Medicine and Rehabilitation .January 2016. Volume 8, Issue 1, Pages 1–10.

Zeckser, J, Wolff, M, Tucker, J, Goodwin, J. “Multipotent Mesenchymal Stem Cell Treatment for Discogenic Low Back Pain and Disc Degeneration”. Stem Cells International. Volume 2016 (2016). Article ID 3908389, 13 pages

Pettine K, Suzuki R, Sand T, Murphy M. Treatment of discogenic back pain with autologous bone marrow concentrate injection with minimum two-year follow-up. National Center for Biotechnology Information. International orthopaedics.2016 Jan. Epub 2015 Jul 10.

Hussein, etal. Effect of autologous platelet leukocyte rich plasma injections on atrophied lumbar multifidus muscle in low back pain patients with monosegmental degenerative disc disease. SICOT J. 2016 Mar 22;2:12.

David Levi MD, Scott Horn DO, Sara Tyszko PA, Josh Levin MD, Charles Hecht-Leavitt MD, Edward Walko DO. “Intradiscal Platelet-Rich Plasma Injection for Chronic Discogenic Low Back Pain: Preliminary Results from a Prospective Trial.” Pain Management. Oxford University Press. Volume , Issue , 24 December 2015. (2015)

W. Shohei, Y. Kuroda, F. Ogura, T. Shigemoto, and M. Dezawa, “Regenerative effects of mesenchymal stem cells: contribution of muse cells, a novel pluripotent stem cell type that resides in mesenchymal cells,” Cells, vol. 1, no. 4, pp. 1045–1060, 2012.

J. M. Gimble, A. J. Katz, and B. A. Bunnell, “Adipose-derived stem cells for regenerative medicine,” Circulation Research, vol. 100, no. 9, pp. 1249–1260, 2007.

P. Ghosh, R. Moore, B. Vernon-Roberts et al., “Immunoselected STRO-3+ mesenchymal precursor cells and restoration of the extracellular matrix of degenerate intervertebral discs: laboratory investigation,” Journal of Neurosurgery: Spine, vol. 16, no. 5, pp. 479–488, 2012.

D. Sakai, J. Mochida, T. Iwashina et al., “Regenerative effects of transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated intervertebral disc,” Biomaterials, vol. 27, no. 3, pp. 335–345, 2006.

D. Sakai, J. Mochida, T. Washina et al., “Differentiation of mesenchymal stem cells transplanted to a rabbit degenerative disc model: potential and limitations for stem cell therapy in disc regeneration,” Spine, vol. 30, no. 21, pp. 2379–2387, 2005.

S. Sobajima, G. Vadala, A. Shimer, J. S. Kim, L. G. Gilbertson, and J. D. Kang, “Feasibility of a stem cell therapy for intervertebral disc degeneration,” Spine Journal, vol. 8, no. 6, pp. 888–896, 2008.

A. Hiyama, J. Mochida, T. Washina et al., “Transplantation of mesenchymal stem cells in a canine disc degeneration model,” Journal of Orthopaedic Research, vol. 26, no. 5, pp. 589–600, 2008.

H. B. Henriksson, T. Svanvik, M. Jonsson et al., “Transplantation of human mesenchymal stems cells into intervertebral discs in a xenogeneic porcine model,” Spine, vol. 34, no. 2, pp. 141–148, 2009.

R. Rajpurohit, M. V. Risbud, P. Ducheyne, E. J. Vresilovic, and I. M. Shapiro, “Phenotypic characteristics of the nucleus pulposus: expression of hypoxia inducing factor-1, glucose transporter-1 and MMP-2,” Cell and Tissue Research, vol. 308, no. 3, pp. 401–407, 2002.

G. Crevensten, A. J. L. Walsh, D. Ananthakrishnan et al., “Intervertebral disc cell therapy for regeneration: mesenchymal stem cell implantation in rat intervertebral discs,” Annals of Biomedical Engineering, vol. 32, no. 3, pp. 430–434, 2004.

B. M. Minogue, S. M. Richardson, L. A. H. Zeef, A. J. Freemont, and J. A. Hoyland, “Characterization of the human nucleus pulposus cell phenotype and evaluation of novel marker gene expression to define adult stem cell differentiation,” Arthritis & Rheumatism, vol. 62, no. 12, pp. 3695–3705, 2010.

C. J. Centeno, “Clinical challenges and opportunities of mesenchymal stem cells in musculoskeletal medicine,” PM&R, vol. 6, no. 1, pp. 70–77, 2014.

A. Condé-Green, R. L. Rodriguez, S. Slezak, D. P. Singh, N. H. Goldberg, and J. Mclenithan, “Comparison between stromal vascular cells' isolation with enzymatic digestion and mechanical processing of aspirated adipose tissue,” Plastic and Reconstructive Surgery, vol. 134, no. 4, p. 54, 2014.

L.-L. Lu, Y.-J. Liu, S.-G. Yang et al., “Isolation and characterization of human umbilical cord mesenchymal stem cells with hematopoiesis-supportive function and other potentials,” Haematologica, vol. 91, no. 8, pp. 1017–1026, 2006.

K. Chen, D. Wang, W. T. Du et al., “Human umbilical cord mesenchymal stem cells hUC-MSCs exert immunosuppressive activities through a PGE2-dependent mechanism,” Clinical Immunology, vol. 135, no. 3, pp. 448–458, 2010.

H. B. Henriksson, M. Thornemo, C. Karlsson et al., “Identification of cell proliferation zones, progenitor cells and a potential stem cell niche in the intervertebral disc region: a study in four species,” Spine, vol. 34, no. 21, pp. 2278–2287, 2009.

H. Brisby, N. Papadimitriou, C. Brantsing, P. Bergh, A. Lindahl, and H. Barreto Henriksson, “The presence of local mesenchymal progenitor cells in human degenerated intervertebral discs and possibilities to influence these in vitro: a descriptive study in humans,” Stem Cells and Development, vol. 22, no. 5, pp. 804–814, 2013.

M. Tanaka, D. Sakai, A. Hiyama et al., “Effect of cryopreservation on canine and human activated nucleus pulposus cells: a feasibility study for cell therapy of the intervertebral disc,” BioResearch Open Access, vol. 2, no. 4, pp. 273–282, 2013.

D. Coric, K. Pettine, A. Sumich, and M. O. Boltes, “Prospective study of disc repair with allogeneic chondrocytes,” Journal of Neurosurgery: Spine, vol. 18, no. 1, pp. 85–95, 2013.

H. J. Meisel, V. Siodla, T. Ganey, Y. Minkus, W. C. Hutton, and O. J. Alasevic, “Clinical experience in cell-based therapeutics: disc chondrocyte transplantation: a treatment for degenerated or damaged intervertebral disc,” Biomolecular Engineering, vol. 24, no. 1, pp. 5–21, 2007.

T. Miyamoto, T. Muneta, T. Tabuchi et al., “Intradiscal transplantation of synovial mesenchymal stem cells prevents intervertebral disc degeneration through suppression of matrix metalloproteinase-related genes in nucleus pulposus cells in rabbits,” Arthritis Research & Therapy, vol. 12, no. 6, article R206, 2010.

S.-H. Yang, C.-C. Wu, T. T.-F. Shih, Y.-H. Sun, and F.-H. Lin, “In vitro study on interaction between human nucleus pulposus cells and mesenchymal stem cells through paracrine stimulation,” Spine, vol. 33, no. 18, pp. 1951–1957, 2008.

S. Strassburg, S. M. Richardson, A. J. Freemont, and J. A. Hoyland, “Co-culture induces mesenchymal stem cell differentiation and modulation of the degenerate human nucleus pulposus cell phenotype,” Regenerative Medicine, vol. 5, no. 5, pp. 701–711, 2010.

S. M. Richardson, R. V. Walker, S. Parker et al., “Intervertebral disc cell-mediated mesenchymal stem cell differentiation,” STEM CELLS, vol. 24, no. 3, pp. 707–716, 2006.

Z. Sun, Z.-H. Liu, X.-H. Zhao et al., “Impact of direct cell co-cultures on human adipose-derived stromal cells and nucleus pulposus cells,” Journal of Orthopaedic Research, vol. 31, no. 11, pp. 1804–1813, 2013.

X. Li, J. P. Lee, G. Balian, and D. G. Anderson, “Modulation of chondrocytic properties of fat-derived mesenchymal cells in co-cultures with nucleus pulposus,” Connective Tissue Research, vol. 46, no. 2, pp. 75–82, 2005.

C. Le Visage, S. W. Kim, K. Tateno, A. N. Sieber, J. P. Kostuik, and K. W. Leong, “Interaction of human mesenchymal stem cells with disc cells: changes in extracellular matrix biosynthesis,” Spine, vol. 31, no. 18, pp. 2036–2042, 2006.

A. W. H. Gebraad, S. Miettinen, D. W. Grijpma, and S. P. Haimi, “Human adipose stem cells in chondrogenic differentiation medium without growth factors differentiate towards annulus fibrosus phenotype in vitro,” Macromolecular Symposia, vol. 334, no. 1, pp. 49–56, 2013.

K. Wuertz, K. Godburn, C. Neidlinger-Wilke, J. Urban, and J. C. Iatridis, “Behavior of mesenchymal stem cells in the chemical microenvironment of the intervertebral disc,” Spine, vol. 33, no. 17, pp. 1843–1849, 2008. D. Sakai, J. Mochida, T. Iwashina et al., “Regenerative effects of transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated intervertebral disc,” Biomaterials, vol. 27, no. 3, pp. 335–345, 2006.

V. Y. L. Leung, D. M. K. Aladin, F. Lv et al., “Mesenchymal stem cells reduce intervertebral disc fibrosis and facilitate repair,” Stem Cells, vol. 32, no. 8, pp. 2164–2177, 2014.

L. Orozco, R. Soler, C. Morera, M. Alberca, A. Sánchez, and J. García-Sancho, “Intervertebral disc repair by autologous mesenchymal bone marrow cells: a pilot study,” Transplantation, vol. 92, no. 7, pp. 822–828, 2011.

Mesoblast Limited, “Positive Spinal Disc Repair Trial Results Using Mesoblast Adult Stem Cells,” 2014,

T. Yoshikawa, Y. Ueda, K. Miyazaki, M. Koizumi, and Y. Takakura, “Disc regeneration therapy using marrow mesenchymal cell transplantation: a report of two case studies,” Spine, vol. 35, no. 11, pp. E475–E480, 2010.

A. Colombini, C. Ceriani, G. Banfi, M. Brayda-Bruno, and M. Moretti, “Fibrin in intervertebral disc tissue engineering,” Tissue Engineering Part B: Reviews, vol. 20, no. 6, pp. 713–721, 2014.

B. R. Whatley and X. Wen, “Intervertebral disc (IVD): structure, degeneration, repair and regeneration,” Materials Science & Engineering C, vol. 32, no. 2, pp. 61–77, 2012.

Y. Wang, Z.-B. Han, Y.-P. Song, and Z. C. Han, “Safety of mesenchymal stem cells for clinical application,” Stem Cells International, vol. 2012, Article ID 652034, 4 pages, 2012.

G. Vadalà, G. Sowa, M. Hubert, L. G. Gilbertson, V. Denaro, and J. D. Kang, “Mesenchymal stem cells injection in degenerated intervertebral disc: cell leakage may induce osteophyte formation,” Journal of Tissue Engineering and Regenerative Medicine, vol. 6, no. 5, pp. 348–355, 2012.

W.-H. Chen, H.-Y. Liu, W.-C. Lo et al., “Intervertebral disc regeneration in an ex vivo culture system using mesenchymal stem cells and platelet-rich plasma,” Biomaterials, vol. 30, no. 29, pp. 5523–5533, 2009.

Y. Zhu, M. Yuan, H. Y. Meng et al., “Basic science and clinical application of platelet-rich plasma for cartilage defects and osteoarthritis: a review,” Osteoarthritis and Cartilage, vol. 21, no. 11, pp. 1627–1637, 2013.

C. S. Lee, O. A. Burnsed, V. Raghuram, J. Kalisvaart, B. D. Boyan, and Z. Schwartz, “Adipose stem cells can secrete angiogenic factors that inhibit hyaline cartilage regeneration,” Stem Cell Research & Therapy, vol. 3, no. 4, article 35, 2012.

T. E. Foster, B. L. Puskas, B. R. Mandelbaum, M. B. Gerhardt, and S. A. Rodeo, “Platelet-rich plasma: from basic science to clinical applications,” The American Journal of Sports Medicine, vol. 37, no. 11, pp. 2259–2272, 2009.

A. S. Wasterlain, H. J. Braun, A. H. S. Harris, H.-J. Kim, and J. L. Dragoo, “The systemic effects of platelet-rich plasma injection,” The American Journal of Sports Medicine, vol. 41, no. 1, pp. 186–193, 2013.

S. C. W. Chan, S. J. Ferguson, and B. Gantenbein-Ritter, “The effects of dynamic loading on the intervertebral disc,” European Spine Journal, vol. 20, no. 11, pp. 1796–1812, 2011.

C. Hohaus, T. M. Ganey, Y. Minkus, and H. J. Meisel, “Cell transplantation in lumbar spine disc degeneration disease,” European Spine Journal, vol. 17, no. 4, pp. S492–S503, 2008.

K. Akeda, H. S. An, R. Pichika et al., “Platelet-rich plasma (PRP) stimulates the extracellular matrix metabolism of porcine nucleus pulposus and anulus fibrosus cells cultured in alginate beads,” Spine, vol. 31, no. 9, pp. 959–966, 2006.

T. Maerz, H. Herkowitz, and K. Baker, “Molecular and genetic advances in the regeneration of the intervertebral disc,” Surgical Neurology International, vol. 4, no. 2, pp. S94–S105, 2013

Hip Pain

Pepke, W, et al. Core Decompression and Autologous Bone Marrow Concentrate for Treatment of Femoral Head Osteonecrosis: A Randomized Prospective Study. Orthop Rev (Pavia). 2016 Mar 21;8(1):6162.

Michalek, J, et al. Autologous adipose tissue-derived stromal vascular fraction cells application in patients with osteoarthritis. Cell Transplant. 2015 Jan 20.

Emadedin M, et al. Long-Term Follow-up of Intra-articular Injection of Autologous Mesenchymal Stem Cells in Patients with Knee, Ankle, or Hip Osteoarthritis. Arch Iran Med. 2015 Jun;18(6):336-44

Hauser, R. Regenerative injection therapy with whole bone marrow aspirate for degenerative joint disease: a case series. Clin Med Insights Arthritis Musculoskeletal Disord. 2013 Sep 4;6:65-72.

Dallari, etal. Ultrasound-Guided Injection of Platelet-Rich Plasma and Hyaluronic Acid, Separately and in Combination, for Hip Osteoarthritis: A Randomized Controlled Study. Am J Sports Med. 2016 Mar;44(3):664-71.

Elbow Pain

Podesta, L., Treatment of partial ulnar collateral ligament tears in the elbow with platelet-rich plasma. Am J Sports Med July 2013.

L Creaney, et al. Growth factor-based therapies provide additional benefit beyond physical therapy in resistant elbow tendinopathy: a prospective, single-blind, randomized trial of autologous blood injections versus platelet-rich plasma injections. Br J Sports Med. 2010.

AK Mishra et al. Efficacy of platelet-rich plasma for chronic tennis elbow: a double-blind, prospective, multicenter, randomized controlled trial of 230 patients. Am J Sports Med. 2014 Feb;42(2):463-71.

MC Glanzmann, Audigé L . Platelet-rich plasma for chronic lateral epicondylitis: is one injection sufficient? Arch Orthop Trauma Surg. 2015 Dec;135(12):1637-45.

Y Raman. Comparison of Local Injection of Platelet Rich Plasma and Corticosteroids in the Treatment of Lateral Epicondylitis of Humerus J Clin Diagn Res. 2015 Jul; 9(7): RC05–RC07.

Arirachakaran A. Platelet-rich plasma versus autologous blood versus steroid injection in lateral epicondylitis: systematic review and network meta-analysis. J Orthop Traumatol. 2016 Jun;17(2):101-12.

Foot/Ankle Pain

Buda, R, et al. "One-step" bone marrow-derived cells transplantation and joint debridement for osteochondral lesions of the talus in ankle osteoarthritis: clinical and radiological outcomes at 36 months. Arch Orthop Trauma Surg. 2016 Jan;136(1):107-16

Giannini, S, et al. One-step bone marrow-derived cell transplantation in talar osteochondral lesions. Clin Orthop Relat Res. 2009 Dec;467(12):3307-20

Hand/wrist Pain

Centeno, CJ, Freeman, MD. Percutaneous injection of autologous, culture-expanded mesenchymal stem cells into carpometacarpal hand joints: a case series with an untreated comparison group. Wien Med Wochenschr. 2014 Mar;164(5-6):83-7

Surgical Augmentation

Murrel, W. Regenerative Treatments to Enhance Orthopedic Surgical Outcome. PM R 7 (2015) S41-S52

Hernigou P1, Flouzat Lachaniette CH, Delambre J, Zilber S, Duffiet P, Chevallier N, Rouard H. Biologic augmentation of rotator cuff repair with mesenchymal stem cells during arthroscopy improves healing and prevents further tears: a case-controlled study. Int Orthop. 2014 Sep;38(9):1811-8.

Vangsness CT Jr1, Farr J 2nd2, Boyd J3, Dellaero DT4, Mills CR5, LeRoux-Williams M5. Adult human mesenchymal stem cells delivered via intra-articular injection to the knee following partial medial meniscectomy: a randomized, double-blind, controlled study. J Bone Joint Surg Am. 2014 Jan 15;96(2):90-8.

Buda, R, F. Vannini,M. Cavallo, B. Grigolo, A. Cenacchi, and S. Giannini, “Osteochondral lesions of the knee: a new one-step repair technique with bone-marrow-derived cells,” Journal of Bone and Joint Surgery—Series A, vol. 92, no. 2, pp. 2–11, 2010.

Gobbi,A, G. Karnatzikos, C. Scotti, V. Mahajan, L. Mazzucco, and B. Grigolo, “One-step cartilage repair with bone marrow aspirate concentrated cells and collagen matrix in full-thickness knee cartilage lesions: results at 2-year follow-up,” Cartilage, vol. 2, no. 3, pp. 286–299, 2011.

Gobbi,A, G. Karnatzikos, and S. R. Sankineani, “One-step surgery with multipotent stem cells for the treatment of large full-thickness chondral defects of the knee,” The American Journal of Sports Medicine, vol. 42, no. 3, pp. 648–657, 2014.

**Note: There exists variation in bio-restorative stem cell and PRP treatments within each of these publications. Taken as a whole they help to guide further research on the topic.