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General Research: Regenerative Medicine and Knee Pain

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Published: Cytotherapy. 2018 Oct;20(10):1238-1246. doi: 10.1016/j.jcyt.2018.08.005. Epub 2018 Oct 11.
Authors: Emadedin M, Labibzadeh N, Liastani MG, Karimi A, Jaroughi N, Bolurieh T, Hosseini SE, Baharvand H, Aghdami N.

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Nineteen patients received bone marrow derived mesenchymal stem cell injections in their knees and twenty four received normal saline injections (placebo). Six months later those that received stem cell treatments experienced significantly greater improvements in pain and function; and could walk further with less pain compared to those patients who received the placebo knee injection. There were no adverse events experienced with those that received the stem cell injection; therefore, they concluded that the stem cell treatment was safe and effective.

Subchondral stem cell therapy versus contralateral total knee arthroplasty for osteoarthritis following secondary osteonecrosis of the knee.

Published: Int Orthop. 2018 Nov;42(11):2563-2571. doi: 10.1007/s00264-018-3916-9. Epub 2018 Mar 27.

Authors: Hernigou P, Auregan JC, Dubory A, Flouzat-Lachaniette CH, Chevallier N, Rouard H.

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All thirty patients received a total knee replacement in one knee; while the other knee received stem cell therapy. The results were as follows: A higher number of thrombolphlebitis was observed on the side of the total knee replacement (15%) versus none on the side with stem cell therapy (0%). At the most recent follow-up (average of 12 years later, some were seen at 8 years others at 16 years), six knees that had a total knee replacement needed subsequent surgery versus only one knee out of 30 needed another stem cell treatment. Twenty one patients (out of 30) preferred the knee that had stem cell therapy. Knees that had stem cell therapy had improvement in cartilage and bone marrow lesions in follow up MRI’s and X-rays. The bottom line? Bone marrow stem cell therapy was an effective long term treatment for knee osteoarthritis with a lower complication rate and a quicker recovery compared to total knee replacement surgery.

Regeneration of meniscus cartilage in a knee treated with percutaneously implanted autologous mesenchymal stem cells.

Published: Med Hypotheses. 2008 Dec;71(6):900-8. doi: 10.1016/j.mehy.2008.06.042. Epub 2008 Sep 10.

Authors: Centeno CJ, Busse D, Kisiday J, Keohan C, Freeman M, Karli D.

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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

Published: Cartilage. 2011 Jul; 2(3): 286–299.

Authors: Alberto Gobbi, Georgios Karnatzikos, Celeste Scotti, Vivek Mahajan, Laura Mazzucco, and Brunella Grigolo

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The study was done to determine the effectiveness of cartilage repair utilizing a 1-step surgery using stem cell therapy from bone marrow combined with a collagen matrix. Patient’s showed significant statistical improvement in all scores at their 2 year follow-up. MRI’s showed cartilage regeneration. No adverse reactions or postoperative complications were noted.

Regenerative Injection Therapy with Whole Bone Marrow Aspirate for Degenerative Joint Disease: A Case Series

Published: Clin Med Insights Arthritis Musculoskelet Disord. 2013; 6: 65–72.

Authors: Ross A. Hauser, MD and Amos Orlofsky, PhD

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Bone Marrow Aspirate in the Treatment of Chondral Injuries

Published: Clin Med Insights Arthritis Musculoskelet Disord. 2013; 6: 65–72.

Authors: James Holton, Mohamed A. Imam, and Martin Snow

General Research: Regenerative Medicine and Shoulder Pain

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The study evaluated the difference between Platelet Rich Plasma therapies compared to procaine for the treatment of frozen shoulder. Sixty patients were randomly divided into two groups. Stretching and exercises were carried out in both groups during the 6 month follow up. The study concluded that PRP for frozen shoulder was superior to and the effects lasted longer than procaine.

Published: In J Clin Pharmacol Ther. 2018 Aug:56(8):366-371.doi:10.5414/CP203262.
Authors: Jonhung Lin.

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The patients who were injected twice were injected 22.33 days apart. Patients who received either one or two treatments reported significant improvements in resting pain, active pain, and functionality score when compared to baseline. These groups also experienced a 42.25% and 50.17% overall improvement respectively. The group that received two treatments experienced statistically more improvements in active pain compared to the group that received one injection. The study concluded that patients diagnosed with shoulder osteoarthritis or rotator cuff tears experienced symptomatic improvements in pain and functionality when injected with BMC or WBM.

Biologic augmentation of rotator cuff repair with mesenchymal stem cells during arthroscopy improves healing and prevents further tears: a case controlled study.

Published: International Orthopaedics (SICOT). 2014 Sep:38(9):1811-8.doi:10.1007/s00264-014-2391-1.

Authors: Hernigou P, Lachaniette CHF, Delambre J, Zilber S, Deffiet P, Chevallier N, Rouard H.

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The 90 patients were split into two groups: 45 patients were injected with bone marrow aspirate concentrate (BMAC) at the time of surgery, and the other 45 patients only had arthroscopic surgery. Mean age was 61. Patients were matched for age, sex, tear size, location and hand dominance. Rotator cuff healing was determined by MRI or CT arthrogram at monthly intervals for the first 2 years and at 10 years. 100% of the shoulders receiving BMAC injection and surgery healed at 6 months. Versus 67% of the shoulders that only received surgery healed at 6 months.

Conventional rotator cuff repair complemented by the aid of mononuclear autologous stem cells.

Published: Knee Surg Sports Traumatol Arthrosc. 2012 Feb; 20(2):373-7.
Authors: Gomes JL, Canquerini da Silva R, Silla LMR, Abreu MR, Pellanda R (2012).

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Single Intra-articular Platelet-Rich Plasma Versus Corticosteroid Injections in the Treatment of Adhesive Capsulitis of the Shoulder: A Cohort Study.

Published: Am J Phys Med Rehabil. 2019 Jul:98(7):549-557.

Authors: Barman A, Mukherjee S, Sahoo J, Maiti R, Rao PB, Sinha MK, Sahoo D, Tripathy SK, Patro BK, Bag ND.

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Sixty patients diagnosed with adhesive capsulitis of the shoulder with less than 6 month duration were placed into two groups. Thirty patients received a PRP injection in the shoulder joint while the other thirty patients received a corticosteroid injection in the shoulder joint. At the 12 week follow up, a single dose of PRP injection was found to be more effective than a corticosteroid injection in terms of improving pain, disability, and shoulder range of motion.

Comparative Efficacy of Platelet Rich Plasma Injection, Corticosteroid Injection and Ultrasonic Therapy in the Treatment of Periarthritis Shoulder

Published: Clinic Diagn Res. May 2017. RC15-RC18.

Authors: Shashank Yeshwant Kothari, Venkataraman Srikumar, Neha Singh.

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Each group had 65 patients. Group A received a PRP injection, Group B received a steroid injection and Group C received ultrasound therapy for 7 minutes every other day for 14 days. All groups were instructed to do exercises that they were taught 2x a day for ten minutes. After 12 weeks the patients in group A that received a PRP injection in their shoulder experienced significant improvement in shoulder range of motion, pain and function compared to those that received a steroid injection or ultrasound therapy.

Comparison between platelet rich plasma injection, corticosteroid injection and short-wave diathermy in the management of pain and the improvement of functional outcome in the patients suffering from adhesive capsulitis of the shoulder: a randomized controlled trial

Published: International Journal of Advances in Medicine 2020 Sep 7(10):1546

Authors:
Debasish Deb, Yumnam Singh Nandabir, Naorem Bimol, Rakesh Das,
Shanavas Anoth Meethal

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50 shoulders representing 47 patients with rotator cuff tears or shoulder osteoarthritis underwent one or two bone marrow concentrate (BMC) or whole bone marrow injections (WBM). The patients who were injected twice were injected 22.33 days apart. Patients who received either one or two treatments reported significant improvements in resting pain, active pain, and functionality score when compared to baseline. These groups also experienced a 42.25% and 50.17% overall improvement respectively. The group that received two treatments experienced statistically more improvements in active pain compared to the group that received one injection. The study concluded that patients diagnosed with shoulder osteoarthritis or rotator cuff tears experienced symptomatic improvements in pain and functionality when injected with BMC or WBM.

Published: Cogent Medicine, 6:1. 2019. DOI:10.1080/2331205X.2019.1628883.
Authors: Marc Darrow, Brent Shaw, Nicholas Schmidt, Gabrielle Boeger & Saksia Budgett, Udo Schumacher (Reviewing editor).

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A case controlled study reported a 10 year follow up on 90 patients who underwent surgery to repair the rotator cuff. The 90 patients were split into two groups: 45 patients were injected with bone marrow aspirate concentrate (BMAC) at the time of surgery, and the other 45 patients only had arthroscopic surgery. Mean age was 61. Patients were matched for age, sex, tear size, location and hand dominance. Rotator cuff healing was determined by MRI or CT arthrogram at monthly intervals for the first 2 years and at 10 years. 100% of the shoulders receiving BMAC injection and surgery healed at 6 months. Versus 67% of the shoulders that only received surgery healed at 6 months.

Published: International Orthopaedics (SICOT). 2014 Sep:38(9):1811-8.doi:10.1007/s00264-014-2391-1.
Authors: Hernigou P, Lachaniette CHF, Delambre J, Zilber S, Deffiet P, Chevallier N, Rouard H.

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14 patients with a mean age of 59.2 received a rotator cuff repair and bone marrow aspirate concentrate was injected during the procedure. MRI performed 12 months postoperatively demonstrated intact repair in all 14 patients. At the one year follow-up, pain and function was significantly improved.

Published: Knee Surg Sports Traumatol Arthrosc. 2012 Feb; 20(2):373-7.
Authors: Gomes JL, Canquerini da Silva R, Silla LMR, Abreu MR, Pellanda R (2012).

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The aim of the study was to compare the effects of one Platelet Rich Plasma (PRP) versus one Corticosteroid injections in patients with adhesive capsulitis of the shoulder. Sixty patients diagnosed with adhesive capsulitis of the shoulder with less than 6 month duration were placed into two groups. Thirty patients received a PRP injection in the shoulder joint while the other thirty patients received a corticosteroid injection in the shoulder joint. At the 12 week follow up, a single dose of PRP injection was found to be more effective than a corticosteroid injection in terms of improving pain, disability, and shoulder range of motion.

Published: Am J Phys Med Rehabil. 2019 Jul:98(7):549-557.
Authors: Barman A, Mukherjee S, Sahoo J, Maiti R, Rao PB, Sinha MK, Sahoo D, Tripathy SK, Patro BK, Bag ND.

Summary

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195 patients diagnosed with periarthritis in the shoulder joint were randomized into three groups. Each group had 65 patients. Group A received a PRP injection, Group B received a steroid injection and Group C received ultrasound therapy for 7 minutes every other day for 14 days. All groups were instructed to do exercises that they were taught 2x a day for ten minutes. After 12 weeks the patients in group A that received a PRP injection in their shoulder experienced significant improvement in shoulder range of motion, pain and function compared to those that received a steroid injection or ultrasound therapy.

Published: Clinic Diagn Res. May 2017. RC15-RC18.
Authors: Shashank Yeshwant Kothari, Venkataraman Srikumar, Neha Singh.

General Research: Regenerative Medicine and Hip Pain

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This is a systemic review of the medical literature to examine the progress of mesenchymal stem cell therapy over the past thirty years for the treatment of early stage osteonecrosis in the hip.

Published: Clinical Orthop Surg. 2016 March; 8(1): 1-8.
Authors: Hernigou P, Trousselier M, Roubineau F, et al.

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Four hip OA patients each had four bone marrow concentrate injections. On average, the last follow-up was administered 3.5 months after the first injection. The results of the case series indicate that patients experienced decreased resting and active pain and had an overall 72.4% improvement. Patients also reported less difficulty with activities of daily living following the procedure.

Published: Clinical Med Insights Case Rep. 2018 August 10.
Authors: Darrow Marc, Shaw Brent, Darrow Brittany and Wisz Stevie.

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Nineteen patients totaling 25 joints (10 knees, 15 hips) were treated with intra-articular bone marrow concentrate for early OA between 2014 and 2016. The mean age was 58 years old. It was concluded that treatment with bone marrow concentrate (which is a mesenchymal stem cell therapy) of early knee or hip OA were safe and demonstrated satisfactory results in 63.2% of patients.

Published: PM R. 2018 Dec; 10(12):1353-1359.
Authors: Rodriguez-Fontan Francisco, Piuzzi Nicolas, Kraeutler Matthew, Pascual-Garrido Cecilia.

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A retrospective study concluded that concentrated autologous bone marrow aspirate can be used as a joint preserving treatment for Osteonecrosis of the femoral head.

Published: BMC Musculoskeletal Disorder. 2109 Sep 5:20(1):410.
Authors: Yohei Tomaru, Tomokazu Yoshioka et al.

General Research: Stem Cell Therapy

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The Basic Science of Bone Marrow Aspirate Concentrate in Chondral Injuries

Published: Orthop Rev (Pavia). 2016 Sep 30;8(3):6659. doi: 10.4081/or.2016.6659. eCollection 2016 Sep 19.

Authors: James Holton, Mohamed Imam, Jonathan Ward, Martyn Snow

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Background: This study examined the quality of bone marrow aspirates extracted using a novel, FDA cleared method to optimally target cells from the inner cortical iliac bone surface without the need for centrifugation. This method employs small draws from a single puncture that promote only lateral flow from multiple sites (SSLM method). The study utilized the Marrow Cellutions bone marrow aspiration system (MC system) which is based on the SSLM method and compared the MC system directly to bone marrow concentrates (BMAC) generated by centrifugation of aspirates harvested with a standard aspiration needle.
Methods: Three direct comparisons were conducted evaluating the SSLM draws and BMACs derived from the same patient from contralateral iliac crests. The levels of TNCs/mL, CD34+ cells/mL, CD117+ cells/mL, and CFU-f/mL were compared between the various bone marrow preparations. The cellular content of a series of SSLM draws was also analyzed to determine the total nucleated cell (TNC) count and the concentration of mesenchymal stem/progenitor cells as measured by colony forming unit fibroblasts (CFU-f).

Results: In direct comparisons with BMAC systems, SSLM draws yielded significantly higher CFU-f concentrations and comparable concentrations of CD34+ and CD117+ cells. In addition, the average quantity of TNCs/mL in a series of 30 patients utilizing the SSLM draw was 35.2 × 106 ± 17.1 × 106 and the average number of CFU-f/mL was 2885 ± 1716. There were small but significant correlations between the TNCs/mL and the CFU-fs/mL using the SSLM method as well as between the age of the patient and the CFU-fs/mL.

Conclusions: The MC Device, using the SSLM draw technique, produced concentrations of CFU-fs, CD34+ cells and CD117+ cells that were comparable or greater to BMACs derived from the same patient. Given the rapid speed and simplicity of the MC Device, we believe this novel system possesses significant practical advantages to other currently available centrifugation based systems.

Keywords: Bone marrow aspirate; Hematopoietic stem cells; Mesenchymal stem cells.

Published: J Transl Med. 2019 Jan 5;17(1):10. doi: 10.1186/s12967-018-1750-x.
Authors: Michael Scarpone, Daniel Kuebler, Andrew Chambers, Carlo Maria De Filippo, Mariangela Amatuzio, Thomas E Ichim, Amit N Patel, Eugenio Caradonna

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Use of centrifuged bone marrow aspirate for regenerative medicine is a growing practice; however, such centrifugation systems require aspirating large volumes (30-240 mL) in order to obtain sufficient stem/progenitor cellularity in a large enough post-centrifugation final volume for therapeutic administration. It is well known that the highest quality (highest quantity of stem/progenitor cells) bone marrow aspirations require aspirating small volumes of bone marrow (1-2 mL). In this study, it was hypothesized that the need for centrifugation, and consequent volume reduction, was due to the limitations of the traditional bone marrow aspiration needle.
Blood and marrow are non-Newtonian fluids and the traditional needle has a large open port at its distal end; as such, it is known that peripheral blood infiltrates bone marrow aspirates greater than 1-2 mL. In this pilot study with Marrow CellutionTM (Ranfac, Avon, MA), a novel bone marrow access and retrieval device requiring substantially less bone marrow aspirate, the limitations of standard bone marrow aspiration needles (e.g., reduced stem/progenitors cell concentrations due to dilution with peripheral blood) were substantially overcome. Further, the singlestep Marrow Cellution produced the same (as counted by CD34+ cells) or greater (as counted by fibroblast-like colony-forming units, CFU-f) stem/progenitor cell concentrations as a combination of traditional needles and centrifugation with the SmartPReP 2 Bone Marrow Aspirate Concentrate® (BMAC) centrifuge-based cellular processing system (Harvest Technologies®, Plymouth, MA). In addition, because there is reduced peripheral blood infiltration in bone marrow harvesting, Marrow Cellution allows the clinician to keep the product entirely on the sterile field rather than requiring the product the leave the sterile field for centrifugation and re-enter the sterile field for administration in the patient, reduces time for the final product to be delivered to the patient (no centrifugation necessary), reduces procedural expenses, and retains all the cells and growth factors obtained in the aspiration.

Authors: David B Harrell, PhD, Brt, OF, FAARM, FRIPH, DABRM; Joseph R Purita, MD, FAAOS, FACS; Raphael Gonzalez, PhD; Leonel Liriano, MD

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