Biopsy needle advancement during bone marrow aspiration increases mesenchymal stem cell concentration

Peters AE, Watts AE.
Front. Vet Science. March 2016.

The authors collected 2 bone marrow aspirates using two different techniques from 12 horses. The first technique was to aspirate BM from a single site with no needle advancement. The second technique was to aspirate BM from multiple sites within the same puncture site by advancing the needle 5mm 3 times, resulting in an aspiration from 4 sites. The needle advancement technique resulted in higher nucleated cell counts, CFUf, and total MSCs. For the single site technique the TNC count/ml assay averaged 14.4 X 10(6); for the multiple site technique, the TNC count assay averaged 20.9 X 10(6) and this increase was statistically significant. For the single site technique the CFU-f assay averaged 33; for the multiple site technique, the CFU-f assay averaged 51 and this increase was statistically significant.


Bone marrow concentrate and platelet-rich plasma differ in cell distribution and interleukin 1 receptor antagonist protein concentration.

Cassano JM, Kennedy JG, Ross KA, Fraser EJ, Goodale MB, Fortier LA.
Knee Surg Sports Traumatol Arthrosc. 2016, January.

This study with 29 patients compared bone marrow aspirate concentrate compositions from the Arteriocyte Magellan device and the Harvest Technologies device with the PRP composition from the Arterioctye Magellan device. The PRP and BMA-C from the Arteriocyte system was compared and there was an 11.8x increase in WBC in BMA-C, a 19x increase in neutrophils in BMA-C, and the platelet concentration was the same in the PRP and BMA-C.  The concentration of PDGF and TGFB  was the same in the Arteriocyte PRP and BMC products.  VEGF was increased the BMA-C by a factor of 4 compared to PRP in the Arteriocyte products.  The concentration of IL-Ira (Interleukin 1 receptor antagonist) was significantly increased in BMA-C over PRP and was above the level needed for a net inhibitory effect on the inflamatory IL1. In comparing the Arteriocyte and Harvest BMC products, they found that there was a significantly greater platelet concentration in the Arteriocyte product.  For CFUs, the Arteriocyte product averaged 41.4 and the Harvest product averaged 32.7 but the difference was NOT statistically significant.


Applying Stem Cells to Orthopedic Conditions.

Kelly FB, Porucznik M.
AAOS Now. 2014 June.

This article, published in an established, peer-reviewed orthopedic surgery journal, summarizes the current and potential benefits of using stem cells in orthopedic surgery.


The use of platelet-rich plasma for the treatment of osteoarthritis.

Jayabalan P, Hagerty S, Cortazzo MH.
Phys Sportsmed. 2014 Sep;42(3):53-62.

In this article the authors review the evidence for the use of PRP in the treatment of arthritis and the clinical outcomes pertaining to its use.


A systematic review of the use of platelet-rich plasma in sports medicine as a new treatment for tendon and ligament injuries.

Taylor DW, Petrera M, Hendry M, Theodoropoulos JS.
Clin J Sport Med. 2011 Jul;21(4):344-52.

Presently, PRP use in tendon and ligament injuries has several potential advantages, including faster recovery and, possibly, a reduction in recurrence, with no adverse reactions described. However, only 3 randomized clinical trials have been conducted.


Application of biologics in the treatment of the rotator cuff, meniscus, cartilage, and osteoarthritis.

Anz AW, Hackel JG, Nilssen EC, Andrews JR.
J Am Acad Orthop Surg. 2014 Feb;22(2):68-79.

Advances in our knowledge of cell signaling and biology have led to the development of products that may guide the healing/regenerative process. Therapies are emerging that involve growth factors, blood-derived products, marrow-derived products, and stem cells.


Muscle and Tendon Injuries: The Role of Biological Interventions to Promote and Assist Healing and Recovery.

Andia I, Maffulli N.
Arthroscopy. 2015 Jan 21. pii: S0749-8063(14)00942-6.

Given the heterogeneity in tendons and tendinopathies, currently, we are not able to decide whether PRP therapies are useful. Despite advances in PRP science, data are insufficient and there is a clear need to optimize protocols and obtain more high-quality clinical data in both tendinopathies and muscle injuries before making treatment recommendations.


Chondrogenic potential of human adult mesenchymal stem cells is independent of age or osteoarthritis etiology

Scharstuhl A, Schewe B, Gaissmaier C, Buhring HJ, Stoop R.

The authors examined stem cells derived from the femoral bone marrow of 98 patients with osteoarthritis.  All stem cells harvested could differentiate into chondrogenic lineage (cartilage cells).  They conclude that a therapeutic application of mesenchymal stem cells (MSC) for cartilage regeneration of osteoarthritis lesions seems feasible.




Regenerative medicine in rotator cuff injuries.

Randelli P, Randelli F, Ragone V, Menon A, D'Ambrosi R, Cucchi D, Cabitza P, Banfi G.
Biomed Res Int. 2014;2014:129515.

Stem cells therapies represent a novel frontier in the management of rotator cuff disease that required further basic and clinical research.


Effectiveness of Platelet-rich Plasma Injection for Rotator Cuff Tendinopathy: A Prospective Open-label Study.

Scarpone M, Rabago D, Snell E, Demeo P, Ruppert K, Pritchard P, Arbogast G, Wilson JJ, Balzano JF.
Glob Adv Health Med. 2013 Mar;2(2):26-31.

A single ultrasound-guided, intralesional injection of PRP resulted in safe, significant, sustained improvement of pain, function, and MRI outcomes in participants with refractory RCT.


Intralesional injection of partial thickness rotator cuff tears

Paper presented at 2014 RSNA meeting in Chicago

A retrospective study with 240 patients in 2 with PRP injection and one with medicine/therapy. MRI done before injecting PRP into tendon defect and at 4 years after injection. For group getting PRP injection: 28% improvement by MRI and 58% improvement by VAS at 4 years.



Efficacy of platelet-rich plasma for chronic tennis elbow: a double-blind, prospective, multicenter, randomized controlled trial of 230 patients.

Mishra AK, Skrepnik NV, Edwards SG, Jones GL, Sampson S, Vermillion DA, Ramsey ML, Karli DC, Rettig AC.
Am J Sports Med. 2014 Feb;42(2):463-71.

No significant differences were found at 12 weeks in this study. At 24 weeks, however, clinically meaningful improvements were found in patients treated with leukocyte-enriched PRP compared with an active control group.


Comparative effectiveness of injection therapies in lateral epicondylitis: a systematic review and network meta-analysis of randomized controlled trials.

Krogh TP, Bartels EM, Ellingsen T, Stengaard-Pedersen K, Buchbinder R, Fredberg U, Bliddal H, Christensen R.
Am J Sports Med. 2013 Jun;41(6):1435-46.

This systematic review and network meta-analysis of randomized controlled trials found a paucity of evidence from unbiased trials on which to base treatment recommendations regarding injection therapies for lateral epicondylitis.


Treatment of partial ulnar collateral ligament tears in the elbow with platelet rich plasma

Podesta L, Crow SA, Volkmer D, Bert T, Yocum LA. Am J Sports Med. 2013 Jul;41(7):1689-1694.

This was a retrospective review of 34 athletes with MRI documented partial thickness UCL tears.  All had failed at least 2 months of nonoperative treatment and an attempt to return to play.  All patients had one injection of PRP at the UCL. Average follow-up was 70 weeks. There were significant decreases in medial elbow joint space opening under valgus stress and in KJOC and DASH outcome scores. 88% returned to same level of play without complaints. 1/34 had persistent UCL instability and had surgery.


Platelet Rich Plasma Can Be Used To Successfully Treat Elbow Ulnar Collateral Ligament Insufficiency In High Level Throwers

Dines JS, Williams PN, ElAttrache N, Conte S, Tomcyzk T, Osbahr DC, Dines DM, Bradley J, Ahmad CS. Am J Orthop. 2016 Jul-Aug;(45), 296-300.

Retrospective review of 44 baseball players (6 pro, 14 college, 24 high school) treated with PRP for partial thickness UCL tears. 16 had 1 injection, 6 had 2 injections, and 22 had three injections.  Average age was 17 years.  Mean time to return to throw was 5 weeks.  Mean time to return to competition was 3 months.  These outcomes are significantly better than previously reported conservative treatment outcomes.



Stem cells and biological approaches to treatment of wrist problems.

Chong AK, He M.
J Wrist Surg. 2013 Nov;2(4):315-8.




Efficacy of ultrasound-guided intra-articular injections of platelet-rich plasma versus hyaluronic acid for hip osteoarthritis.

Battaglia M, Guaraldi F, Vannini F, Rossi G, Timoncini A, Buda R, Giannini S.
Orthopedics. 2013 Dec;36(12):e1501-8.

Intra-articular injections of PRP are efficacious in terms of functional improvement and pain reduction but are not superior to HA in patients with symptomatic hip OA at 12-month follow-up.


Hip osteoarthritis in dogs: a randomized study using mesenchymal stem cells from adipose tissue and plasma rich in growth factors.

Cuervo B, Rubio M, Sopena J, Dominguez JM, Vilar J, Morales M, Cugat R, Carrillo JM.
Int J Mol Sci. 2014 Jul 31;15(8):13437-60.

Our findings show that aMSCs and PRGF are safe and effective in the functional analysis at 1, 3 and 6 months; provide a significant improvement, reducing dog's pain, and improving physical function. With respect to basal levels for every parameter in patients with hip OA, aMSCs showed better results at 6 months.



Effect of leukocyte concentration on the efficacy of platelet rich plasma in the treatment of knee osteoarthritis

Riboh JC, Saltzman BM, Yanke AB, Fortier L, Cole BJ.
American J Of Sports Med.  March 2016. 44(3): 792-800.

This is a level 2 Meta-Analysis study of 6 level 1 studies and 3 level 2 studies.  The total number of patients is 1055. Leukocyte poor platelet rich plasma (LP-PRP) resulted in improved functional scores compared to hyaluronic acid or placebo or leukocyte rich platelet rich plasma (LR-PRP).  All 3 groups had similar subjective  IKDC score improvements.


Efficacy of Intra-articular PRP Injections In Knee Osteoarthritis : A Systematic Review

Meheux, CJ, McCulloch PC, Lintner DM, Varner KE, Harris JD.
Arthroscopy. Mar 2016. 32(3). Pp 495-505.

This paper is a level 1 meta-analysis of 6 human, in vivo, Level 1 studies. In patients with symptomatic knee OA, PRP injections resulted in significant clinical improvements up to 12 months postinjection. Clinical and WOMAC scores were better with PRP versus HA from 3-12 months postop. This meta-analysis did not evaluate LP-PRP and LR-PRP or steriods in this study.


Viscosupplementation for Osteoarthritis of the Knee: A Systematic Review of the Evidence

Jevsevar D, Donnelly P, Brown GA, Cummins DS.
JBJS. 2015 Dec 16; 97(24): 2047-60.

Meta-analysis of only the double-blinded, sham-controlled trials with at least sixty patients did not show clinically important differences of HA treatment over placebo. When all literature was added to the analysis, the overall effect was greater but was biased toward stronger treatment effects because of the influence of nonblinded or improperly blinded trials.


Adult human mesenchymal stem cells delivered via intra-articular injection to the knee following partial medial menisectomy: a randomized, double blind, controlled study.

Vangsness CT, Farr J, Boyd J, LeRoux-Williams M, et al.
JBJS. 2014 Jan 15;96(2):90-98.

At 12 months post arthroscopic partial menisectomy, there was evidence of significant meniscus regeneration and improvement in knee pain following single dose treatment with allogeneic mesenchymal stem cells (MSCs).  The largest increase in meniscal volume was seen in patients receiving the lower of two tested doses of MSCs (50,000,000 stem cells).


Concentrated bone marrow aspirate improves full thickness cartilage repair compared with microfracture in the equine model

Fortier LA, Potter HG, et al.
JBJS. 2010 Aug 18;92(10):1927-1937.

Delivery of bone marrow aspirate concentrate can result in healing of acute full thickness cartilage defects that is superior to that of microfracture alone in an equine model.


"Regenerative repair of damaged meniscus with autologous adipose tissue-derived stem cells."

Pak J, Lee JH, Lee SH.
Biomed Res Int. 2014;2014:436029.

Here, we present a review, highlighting the possible regenerative mechanisms of damaged meniscus with MSCs (especially adipose tissue-derived stem cells (ASCs)), along with a case of successful repair of torn meniscus with significant reduction of knee pain by percutaneous injection of autologous ASCs into an adult human knee.


Knee Osteoarthritis Injection Choices: Platelet- Rich Plasma (PRP) Versus Hyaluronic Acid (A one-year randomized clinical trial).

Raeissadat SA, Rayegani SM, Hassanabadi H, Fathi M, Ghorbani E, Babaee M, Azma K.
Clin Med Insights Arthritis Musculoskelet Disord. 2015 Jan 7;8:1-8.

This study suggests that PRP injection is better than hyaluronic acid injection in reducing symptoms and improving quality of life and is a therapeutic option in select patients with knee arthritis who have not responded to conventional treatment.


Does intra articular platelet rich plasma injection improve function, pain, and quality of life in patients with osteoarthritis of the knee?  A randomized clinical trial. 

Rayegani SM, Raeissadat SA, Taheri MS, Babee M, Bahrami MH, Eliaspour D, Ghorbani E.
Orthop Rev (Pavia). 2014 Sep 18;6(3):5405.

This randomized clinical study looked at patients with knee arthritis. 31 patients had 2 PRP injections one month apart and 31 patients had no PRP injections.  Both groups had physical therapy.  The PRP group had statistically significant better WOMAC and SF-36 scores 6 months after treatment.



Plasma rich in growth factors (PRGF) as a treatment for high ankle sprain in elite athletes: a randomized control trial.

Laver L, Carmont MR, McConkey MO, Palmanovich E, Yaacobi E, Mann G, Nyska M, Kots E, Mei-Dan O.
Knee Surg Sports Traumatol Arthrosc. 2014 Jun 18

Athletes suffering from high ankle sprains benefit from ultrasound-guided PRP injections with a shorter RTP, re-stabilization of the syndesmosis joint and less long-term residual pain. LEVEL OF EVIDENCE: II.


A single platelet-rich plasma injection for chronic midsubstance achilles tendinopathy: a retrospective preliminary analysis.

Murawski CD, Smyth NA, Newman H, Kennedy JG.
Foot Ankle Spec. 2014 Oct;7(5):372-6.

A retrospective evaluation of patients receiving a single PRP injection for chronic midsubstance Achilles tendinopathy revealed that 78% had experienced clinical improvement and had avoided surgical intervention at 6-month follow-up.