1

PRP, BMAC, Stem cells The Basics

Jim Bradley M.D.Clinical Professor Orthopedics UPMC

Head Team Physician – Pittsburgh Steelers Consultant – Miami Marlins

Justin Arner MD Resident UPMC

Cellular Treatment Hierarchy

Platelet Rich Plasma

Buffy Coat

Leukocyte Enriched

Plasma Based

Leukocyte Poor

Stem Cells

AutologousPOC vs.

Expanded

Marrow Adipose

Allogeneic

Adipose Marrow Cord/Amnion

Algorithm of Orthobiologics 2018

The Bio Buzz…

Platelet Rich Plasma Stem Cells Orthokine/Regenokine/IRAP

Growth factors from platelets & factors in the plasma that modulate the healing process.

• Large amount of literature (Level 1&2)• Better understanding of best PRP form

Multipotent cells, able to differentiate into several cell lineages.

Clinical use in orthopedics is increasing specifically for cartilage issues

Anabolic and inhibitory cytokines taken from incubated monocytes

• Very little clinical data• High cost/hype• Not cleared in the US• Requires blood banking • Any benefits over PRP?

2

The Top 10 Things you need to know about PRP & Stem cells

#1 There are Critical Obstacles to Widespread

Biologic TxRegulatory Pathway

Point of care cellular Tx Minimal manipulation Autologous Efficacy not related to the metabolic activity of the cells

Research High level comparative studies (millions $$$) Used in many applications, need data on all indications

Reimbursement Coding for some products in not available Deemed “Experimental” by Ins. Co. Individual approvals

FDAIndications to date: “an orthopedic surgical site”

3

Legality

NFLMLBNHLNCAAWADA

GOOGLE Sites 2018 PRP - 19,100,000

Stem cells - 93,500,000PRP - 20,100,000Stem Cells - 103,000,000

#2 Definition of PRP

Platelet-Rich

Plasma

Autologous plasma fraction that has a concentration of platelets above

baseline (200,000 platelets/uL)1

Autologous concentration of

platelets in a small volume of plasma.2

Plasma fraction with a concentration of at

least 1,000,000 platelets/uL.3

1. L. Mazzucco, V. B., E. Cattana, R. Guaschino, P. Borzini,: Not every PRP-gel is born equal Evaluation of growth factor availability for tissues through four PRP-gel preparations: Fibrinet, RegenPRP-Kit, Plateltex and one manual procedure. , 2009.

2. Marx, R. E.: Platelet-rich plasma: evidence to support its use. Journal of Oral and Maxillofacial Surgery, 62(4): 489-496, 2004.3. Marx, R.E. Platelet-Rich Plasma (PRP): What is PRP and what is not PRP? Implant Dentistry, 10(4): 225-228, 2001.

There is None

4

Robert Marx, D.D.S. “definition” of PRP platelet concentration

“incorrectly quoted as dogma” 2001 White Paper in Implant Dentistry1

Minimum 1,000,000 platelets/µL = 5x PRP Whole blood baseline – 1.5 -2 x 105 platelets µL

NO supporting citations or references

1. Marx RE. Platelet-rich plasma (PRP): what is PRP and what is not PRP? Implant Dent. 2001;10(4):225-8.

2. Marx RE, Carlson ER, Eichstaedt RM, Schimmele SR, Strauss JE, Georgeff KR. Platelet-rich plasma: Growth factor enhancement for bone grafts. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1998 Jun;85(6):638-46.

Definition of PRP

High concentrations (6-11x) may have a paradoxically inhibitory effect

1. Weibrich G et al. Effect of platelet concentration in platelet-rich plasma on peri-implant bone regeneration. Bone 2004; 34(4): 665-671.2. Choi et al. Effect of PRP concentration on the viability and proliferation of aveolar bone cellsInter J Maxillofac Surg. 20053. Graziani F et al. The in vitro effect of different PRP concentrations on osteoblasts and fibroblasts. Clin Oral Impl Res 2006; 17: 212-219.

Optimal Concentration of Platelets is Unknown !!!

Viability & proliferation of cells was suppressed by high concentrations but increased by moderate concentrations. 2

It may be different for different pathologies

1. Concentration of platelets to bind the available GF receptors without oversaturation

2. Triggering a positive proliferative response3. Without inducing a negative feedback inhibition4. Receptor levels may vary between tissues

therefore ideal PRP concentrations may as well

What is the Optimal Concentration of Platelets?

5

#3 All Current Systems are NOT the same

ACP, Biomet GPS, PReP, MTF cascade, Harvest & Magellan

Differences in blood volume, centrifuge rate/time, delivery method, activating agent, WBC count, PRP volume, Platelet & GF concentration

What do we have today ?

Buffy coat based PRP systems GPS Harvest Magellan

Plasma based PRP systems ACP Cascade BTI (Anitua/Sanchez)

All use platelet GF release What differs is WBC’s, RBC’s & plasma

concentrations

#4 PRP is EXTREMELY Complex

Delivery methods Activate +/-

Plasma-based vs. Buffy coat White cells +/-

Dozens of commercially available systems (40) Variable spin protocols & cellular milieu product

Significant variability in cellular concentrations Vs. systems Vs. individuals Vs. SAME individual

Frequency of dosing Acute vs. Chronic? Anatomic site specific?

6

Alpha granules

Platelet activators

Meta‐analysis

WBC content

Exogenous activation

Clotting factors

Spray

Neutrophil rich

Buffy coat systems

Plasma based systems

Neutrophil poor

Delivery technique

Hydrogel

Endogenous activation

Thrombin

Ultrasound guided injections

Clot/Scaffold 

Ca2Cl + Thrombin

Tissue specific

Baseline Levels

Activation Method

Varied [platelets/μL]

Erythrocytes

Ca2Cl

Type I Collagen

> 1,250,000 platelets/μL

> 750,000 to 1,250,000 platelets/μL

> Baseline to 750,000 platelets/μL

Platelet‐poor plasma

Dense granules

Fibrinogen levelsGrowth factor levels

Spin Protocol

Varied individual  platelet count

Preparation method

Platelet aggregation

pH

Local anesthetics

Anticoagulants

Anti‐oxidant response

Dosing Frequency

Delivery platform

Antimicrobial effect

Inflammation

Cytokines

Ideal anatomic location

Closed procedure

Open procedure

ChronicAcute 

Growth factor kinetics

Platelet‐rich plasma

Multitude of Variables Contribute to Mixed Results

#5 PRP: A Previous Decade of Flawed Research Methodology??

#6 The Fundamentals Have Been Missed!!

Back to the Fundamentals : the beginning of the PAW system

7

… and It can get VERY complicated

Platelet Rich Plasma: The PAW Classification System: Arthroscopy Vol 28 No. 7 July 2012

P2 n I B beta

#7 Where ?

OVERALL Office Experience

Total > 450 patients 90% Athletes - > 900 injections 250 lower extremities injuries 200 upper extremities injuriesNFL, MLB, NHL (30%)

Only injection code used Recently had to charge $200/injection

8

Clinical ApplicationsMy Experience

Knee Disorders

• DJD

• MCL/LCL sprains

• Patellar Tendonitis

• Symptomatic Bipartite Patella

Ankle/LE Disorders

• Achilles Tendonitis

• Ankle Sprain (ATFL)

• Peroneal tendons

• Soleus Muscle Strain

• High Ankle Sprains

Soft Tissue LE Disorders

• Rectus Strain

• Proximal Hamstring Strain ( Ct guided )

• Mid/Distal Hamstring Strain

Clinical Applications

Shoulder Disorders

• Shoulder DJD

• Rot (prct) Cuff Tears

• Rotator Cuff Tendinopathy

• SLAP Lesions

• AC Separation

Elbow Disorders

• UCL (partial) tear

• Med/Lat Epicondylitis

• OCD lesions

My Clinical Protocol

ACP - 1 injection a wk for 3wks if better after 2 no more

Start 24-48 hrs after acute injuryNo changes rehab protocol

9

Office Overall Outcomes

Successful outcome = Resolution of symptoms, asymptomatic return to play, no surgery

Poor outcome = Recurrence of symptoms, inability to return to play, surgery

Outcomes/Success RateKnee

Good

Not GoodGood

Not Good

Good

Not Good

MCL 100% DJD 74%

Patellar Tendon 43%

Formulation Specific ResultsAuthor Diagnosis Formulation Outcome

Patel, AJSM 2013 Knee OA Leukocyte poor Significant difference

Filardo, Musk.Disord 2012

Knee OA Leukocyte rich No difference

Cerza, AJSM 2012 Knee OA Leukocyte poor Significant difference

Sanchez, Arthro2012

Knee OA Leukocyte poor Significant difference

Spakova, Am J Phys Med Rehab 2012

Knee OA Leukocyte poor Significant difference

Filardo, KSSTA 2012

Knee OA Leukocyte rich No difference

2014 TOBI, PRP Symposium Jason Dragoo, MD

10

Intra-articular Autologous Conditioned Plasma Injections Provide Safe and Efficacious Treatment for Knee Osteoarthritis

An FDA-Sanctioned, Randomized, Double-blind,Placebo-controlled Clinical Trial

Patrick A. Smith, MDInvestigation performed at the Columbia Orthopedic Group, Columbia, Missouri, USA

ACP is safe & provides quantifiable benefits for pain relief & functional improvement with regard to knee OA.

No adverse events were reported for ACP administration.

After 1 yr, WOMAC scores for the ACP subjects had improved by 78%

from baseline score, whereas placebo group had improved by 7%

AJSM 2016

Other joints affected with OA may also benefit from this Tx.

Systematic review of level I evidence of PRP for knee OA

5 RCT’s with 575 pts

4 studies PRP vs. HA, 1 study 1 vs 2 PRP vs saline

PRP use in OsteoarthritisA Systematic Review of Randomized Controlled Trails

Sherman B, Bradley J, Mandelbaum B,

Overall they showed sig. improvements in pain, stiffness, & joint function vs baseline HA, & saline

Level 1, RCT

US guided PRP/dry needling vs dry needling alone

12 wk f/u

PRP with significantly better VISA score

25.4 improved vs 5.2 with needling alone

No treatment failures in PRP group

The American Journal of Sports Medicine, Vol. 42, No. 3

11

Level 4, Case series 28 athletes

17 professional 11 semiprofessional

*Chronic, failed conservative tx PRP injection x 3 2 yr f/u Significantly improved VISA, VAS, and lysholm scores 16 pts (57%) returned to completely normal Only 3 needed surgery

The American Journal of Sports Medicine, Vol. 42, No. 4

My top 4 LE office favorites

1. Early OA

2. MCL/LCL sprains

3. Early splits in the post/med menisco-capsular junction

4. Elbow partial UCL

What does the Literature say about shoulder & PRP?

12

Positive effectAuthor Yea

rJournal

Level of evidence

Investigation Effect N Avg f/u (mo.)

Limitations

Ebert 2017 AJSM 1 PRP effect on double row SS repairs ≤ 20mm(2 injections @ 7 & 14 days)

PRP:-Significant postop clinical improvements.-High level pt satisfaction.-Greater max abd strength @ midterm f/u.

6 42 -PRP components not measured.-The reported [Platelet] was obtained from the general commercial system info.-All [Platelet], [WBC], & [GF] from individual pts were assumed to be the same.-Tendon quality was evaluated via subjective measures.-Results not correlated with larger or multiple tears, or single-row repair.-Pts were not blinded to their randomization (+/- post-op injection).-Study did not evaluate or report on return to sport involving higher demand upper limb movements.

Sengodan 2017 J Clin Imaging Sci

2 U/S guided L-PRP effect on Partial RCTs (52% Traumatic 48% Degenerative)

L-PRP: -Markedly improved clinical, radiological, and functional shoulder outcomes.

20 2 -PRP components not measured or reported.-Various tear etiologies, types, and locations.-No control group.-Small sample size.-Short f/u.

Kim 2017 Cell Transplant

2 BMAC-PRP effect on TDSCs &Partial RCTs non-responsive to conservative tx

BMAC-PRP: -Enhancedproliferation/migration of TDSCs & prevents aberrant chondrogenic

12 3 -PRP components not measured.-TDSCs from a single donor.-No control group.-Small sample size.-Short f/u.

Positive effectAuthor Yea

rJournal

Level of evidence

Investigation Effect N Avg f/u (mo.)

Limitations

Ebert 2017 AJSM 1 PRP effect on double row SS repairs ≤ 20mm(2 injections @ 7 & 14 days)

PRP:-Significant postop clinical improvements.-High level pt satisfaction.-Greater max abd strength @ midterm f/u.

6 42 -PRP components not measured.-The reported [Platelet] was obtained from the general commercial system info.-All [Platelet], [WBC], & [GF] from individual pts were assumed to be the same.-Tendon quality was evaluated via subjective measures.-Results not correlated with larger or multiple tears, or single-row repair.-Pts were not blinded to their randomization (+/- post-op injection).-Study did not evaluate or report on return to sport involving higher demand upper limb movements.

Sengodan 2017 J Clin Imaging Sci

2 U/S guided L-PRP effect on Partial RCTs (52% Traumatic 48% Degenerative)

L-PRP: -Markedly improved clinical, radiological, and functional shoulder outcomes.

20 2 -PRP components not measured or reported.-Various tear etiologies, types, and locations.-No control group.-Small sample size.-Short f/u.

Kim 2017 Cell Transplant

2 BMAC-PRP effect on TDSCs &Partial RCTs non-responsive to conservative tx

BMAC-PRP: -Enhancedproliferation/migration of TDSCs & prevents aberrant chondrogenic

12 3 -PRP components not measured.-TDSCs from a single donor.-No control group.-Small sample size.-Short f/u.

Positive effectAuthor Yea

rJournal

Level of evidence

Investigation Effect N Avg f/u (mo.)

Limitations

Tahririan 2016 Adv Biomed Res

2 U/S guided PRP effect on Pts with <1cm partial RCTs (bursal side) non-responsive to conservative tx

Single PRP injection:-Reduced pain & improved ROM in pts w/ bursal side partial RCT who failed to respond to conservative tx.-Data showed the effectiveness of PRP injection reduces by age.

17 3 -Platelets were measured but WBC count was not.-No control group.-Non-randomized.-Small sample size.-Short f/u.

D’Ambrosi 2016 Musculoskel Surg

1 PRP effect on Degenerative full-thickness SS tears (grade C2-C3)

PRP: -Reduces pain @ short-term f/u, allowing more rapid recovery of mobilization & improved function.-No significant difference in DASH score or U/S after 6 mo.

40 6 -Measured pts baseline [Platelet] but did not measure PRP components.-No placebo group.-Short f/u.

Lädermann 2016 Orthop Traumatol Surg Res

2 L-PRP clinical & radiologic effects on SS interstitial RCTs

L-PRP: -Showed significant and clinically relevant effect on RCT size and clinical parameters.

25 6 -PRP components not measured.-The reported [Platelet] was obtained from the general commercial system info.-All [Platelet], [WBC], & [GF] from individual pts were assumed to be the same

13

Positive effect

Author Year

Journal

Level of evidence

Investigation

Effect N Avg f/u (mo.)

Limitations

Holtby 2016 OJSM 1 PRP effect on repair of Full thickness Small-to-Medium (≤ 3cm) RCTs

PRP: -Significantly improvedperioperative pain short-term (days 8-11). -PRP group also reported taking less painkillers than control group (days 0-30).-But no significant impact on ptoutcome measures or structural integrity of repair compared with control group.

82 6 -PRP components not measured or reported.-Small sample size.-Short f/u.

Zhang 2015 Act Orthop Traumatol Turc

1 PRP effect on double row SS repair

Local PRP injection:-Double-row RC repair resulted in lower recurrence rates than RC repair control without PRP.

60 12 -PRP components not measured or reported.-Short f/u.-Majority of patients in the database were in a similar geographical region.-Limited to Non-Medicare pts (<65yo).

Positive effect

Author Year Journal

Level of evidence

Topic Effect N Avg f/u (mos)

Limitations

Shams 2016 Eur J Ortho SurgTrauma

2 PRP vs. Corticosteroid for partial RC tears

PRP group showed better earlier results but no statistical difference after 6 months

40 6 wks3 mo6 mo

???

Pandey 2016 JSES 1 Moderate [PRP] for medium to large RC tears

PRP improved clinical and structural outcomes in large tearsAlso enhanced vascularity in early phase

102 24??? PRP agitated Stored 1 day at room temp before use

Jo 2015 AJSM 1 Leukocyte poor PRP & cuff repair

Improved retear rates, cross sectional area

74 12 Single blind, arbitrarily used PRP concentration

Cross 2015 AJSM n/a (Lab) PRP & rotator cuff tendinopathy

Positive effect for leukocyte reduced PRP on healing of moderate cuff tendinopathy

20 n/a Cadaveric study

Ilhanli 2015 Iran red crescent med J

4 PRP vs PT for chronic SS tears

Higher DASH scores 62 12 No description of PRP growth factor concentration

Positive effect

Author Year Journal Level of evidence

Topic Effect N Avg f/u Limitations

Zumstein 2014 JSES 1 Leukocyte & platelet rich fibrin & cuff repair

Significantly improved vascularization

20 3 Small sample, no long term f/u

Jo 2013 AJSM 1 PRP gel & cuff repair

Improved retear rates, cross sectional area in large/massive tears

46 12 Small sample, short f/u, arbitrary concentration of PRP

Rha 2013 Clin Rehabil 1 PRP vs dry needle in partial RTC tear

Superior outcome scores and pain

39 6 Short f/u

Scarpone 2013 Glob Adv Health Med

3 Leukocyte rich PRP & RTC tendinopathy

Improved outcomes and satisfaction

17 12 Leukocyte rich, no control group

Gumina 2012 JBJS 1 PLM & large/massive cuff tears

Improved repair integrity but no difference in outcomes

80 13 <2 yr f/u

14

Positive effect

Author Year Journal Level of evidence

Topic Effect N Avg f/u Limitations

Barber 2011 Arthroscopy 3 PRFM & Cuff repair

Improved retear rates and Rowe scores w/PRFM

40 31 Sample size, lack of randomization

Randelli 2011 JSES 1 PRP & Rotator cuff repair

Reduced pain in first few postoperative months

53 24 Unknown quantity of platelets & growth factors

Neutral/Negative effectAuthor Year Journ

alLevel of evidence

Topic Effect N Avg f/u (mos)

Limitations

Gwinner 2016 Arch Ortho Trauma Surg

3 Two-staged PRP application to RC repair

No significantimprovement but trend for lower retear rates

36 24 ???

Flury 2016 AJSM 1 PRP vs. Ropivacaine (local anesthetic)

PRP group showed no significant functional improvement

120 24 No description of growth factor concentration only 1 injection platelet concentration unknown dilution with NaCl

Say 2016 J Ortho Surg

3 Single dose of PRP vs. steroid for subacromialimpingement sydrome

Steroid injection was more effective than PRP in Constant score and VAS pain

60 6 wks6 mo

PRP was prepared manually using single spin rotation.Reported 4 fold increase but did not report actual [platelets/μL]

Verhaegen 2016 JSES 2 Arthroscopic needling for RC augmented with PRP

PRP group showed no beneficial effect on RC healing

40 3 mo6 mo1 yr

No description of growth factor concentration, leukocyte-rich prp, short F/U

Wehren 2015 KSSTA 3 ACP vs cortisone subacromial injections for partial RTC tears

Early improvement in outcomes w/ACP but no difference at 6 months

50 6 No description of growth factor concentration

Hak 2015 Sports Health

2 PRP & Rotator cuff repair

No diff in outcomes 23 6 wks No description of growth factor concentration, short f/u

Wang 2015 AJSM 1 PRP & Rotator cuff repair

No improvement in outcomes/tendon healing

60 16 wks No exact determination of growth factor concentration, short f/u

Author Year Journal Level of evidence

Topic Effect N Avg f/u (Mos)

Limitations

Carr 2015 AJSM 1 Leukocyte rich PRP & acromioplasty

No diff in outcomes, reduced cellularity & vascularity

60 24 Leukocyte rich PRP, one injection, biopsy 12 weeks post injection

Malavolta 2014 AJSM 1 PRP liquid w/thrombin

No improvement in retear rates or clinical outcomes

54 24 Platelet poor plasma used, injected before portals were closed

Werthel 2014 Int J Shoulder Surg

2 Leukocyte poor ACP & cuff repair

No improvement in retear rates or outcomes

65 19 No description of growth factor concentration, differing amts of ACP injected

Charousset 2014 Arthroscopy 3 PRP & Rotator cuff repair

No diff in outcomes, recurrent tear rate or healing rate

61 28.6 No description of growth factor concentration, underpowered, single injection

Antuna 2013 Acta Orthop Belg

1 PRF and larg/massive cuff repairs

No diff in clinical outcomes/retear rates

28 >24 Small sample size

Weber 2013 AJSM 1 PRFM & cuff repair

No improvement in structural integrity, perioperative morbidity or outcomes

60 16 wks No description of growth factor concentration, short f/u

Neutral/Negative effect

15

Author Year Journal Level of evidence

Topic Effect N Avg f/u (Mos)

Limitations

Ruiz-Moneo 2013 Arthroscopy

1 Leukocyte poor PRGF & cuff repair

No diff in healing or postop outcomes

38 12 No exact determination of growth factor concentration, small sample, short f/u

Kesikburun 2013 AJSM 1 PRP & cuff tendinopathy

No diff in QOL, pain, ROM

40 12 No description of growth factor concentration, short f/u

Rodeo 2012 AJSM 2 PRFM and cuff repair

Negative effect on healing, no diff in outcomes

79 12 No description of growth factor concentration, short f/u

Bergeson 2011 AJSM 3 PRFM and cuff repair

No diff in outcomes. Higher retear rates and higher infection rates

37 27 (13 in PRFM group)

No description of growth factor concentration, small sample, large diff in f/u between groups

Castricini 2011 AJSM 1 PRFM & cuff repair

No improvement in retear rates or tendon healing

88 16 No description of growth factor concentration

Jo 2011 AJSM 2 PRP gel & cuff repair

No improvement in pain, ROM, outcome scores, retear rates

42 19 Short f/u, arbitrary use of PRP volume, PRP collected 1 day prior to surgery

Neutral/Negative effect

Every Study shown - positive, negative & neutral has flaws &

some fatal“It basically has been 10 years of failed methodology”

So, where does this leave us?

Decrease in retear rates for small & medium sized RC tears.

Large & Massive…still a problem

16

#8 Practical Basic Science studies over the last 6 years

Basic Science University of Connecticut Human Soft Tissue Research Lab

Mazzocca G, McCarthy B, Romeo A, Bradley J, Arciero R 2009 -17

PRP the basicsUse plasma based (low WBC’s)

Platelet # does not make a difference (3X)

GF’s vary everyday

Platelet to WBC ratio is key (2000:1)

Steroids deactivate AG

Caines kill everything

NSAIDs don’t make a difference Antibiotic & Anti-inflammatory

Modifies post op pain

Multiple injections better one /wk x 3

ACP HA Toradol work synergistically in OA

17

O.R. Experience

Have used all the major PRP systems in the OR

Top 3 UE ACP OR favorites

1. RCR

2. RC revision

3. Revision Labral repairs

Post-op Pain relief is the major indication

Significant reduction in narcotic use

#9 Stem Cells are here to stay!

18

My Clinical Protocol

BMAC - 1 injection with or without scope usually mild to mod OA knee2% Hct 7ccs + PRP 3cc

Adult

Hematopoietic

Peripheral blood

Mesenchymal

Mesoderm

SynoviumAdipose PeriosteumBone

marrow

Germ

Sperm/Egg

Embryonic

Fetus

Not approved for use in

orthopaedics

Classification of Stem Cells

Cell Source

Cell Type

Tissue Source

Tissue Type

MSC’s What the heck are they?

Unspecialized cells with a self renewal potential which can differentiate into different adult cell types (mesenchymal tissue)

Can exert regulatory effect on local & distant cells

Can be isolated from almost every tissue

Found as perivascular cells

Secrete massive levels of immunomodulatory & trophic substances

Modulate T-cell response

19

Improve healing by a synergistic Triple Action Mechanism

1. Direct participation in repair (diff into damaged or lost cells)

2. Stimulation of local cells via paracrine mechanism (indirectly promote vascularization, proliferation & differentiation via soluble factors)

3. Anti-inflammatory or immunomodulatory activity (modulate inflammatory cascade)

It May not be their ability to differentiate

• MSC’s are the body’s “Drug Store” Trophic properties

• Anti-inflammatory, Anti-apoptotic, Anti-microbial

• Induce cell proliferation & angiogenesis, reduce scar formation

• Locally derived SC maybe more effective than other sources

MSC’s most relevant contribution maybe is to provide a suitable microenvironment for tissue repair not direct repair

Recent In vivo MSC studiesStudy N F/U

Mean Age

Cells Result Conclusion

Koh et al.2014

37 26.5 months

57.4 Buttock Fat pad Mean 3.8x106

• IKDC & Tegner significantly improved (P < .001)

• 94% good to excellent results• 76% of repairs abnormal or severely

abnormal by ICRS

Despite lack of lesion healing, improvement in pain & function. Poorer outcomes with large lesions & high BMI

Koh et al.2013

18 24.3 months

54.6 Infrapatellarfat padMean 1.18x106 with PRP

• WOMAC improved from 50 to 30 (P < .001)

• Lysholm improved from 40 to 73 (P < .001)

• VAS improved from 4.8 to 2.0 (P < .005)

Intra-articular injection of AD MSC is effective inimproving pain & function

Jo et al.2014

18 6 months

18-75 Abdominal FatLow 1.0x107

Med 5.0x107

High 1.0x108

High dose group only• WOMAC improved @ 6 months• Size of cartilage defect decreased

(arthroscopy)• Volume of cartilage increased (histology)

Intra-articular injection of 1.0x108 AD MSC intoknee with OA improved function & pain

Xie et al.2014

42 12 weeks

Rabbit 1. BMSC + PRP

2. ADSC + PRP

BMSC + PRP showed:• Higher proliferation rate & higher

expression of cartilage-specific genes/proteins than ADSC

• Improved gross appearance, subchondralbone regeneration, and histological & immunohistochemical characteristics

PRP as a scaffold for stem cells is synergistic for chondrocyte proliferation & viability

20

Why Concentrate Bone Marrow?

Angel BMC at 96 hrs.BMA at 96 hrs.

Healing trinity: Cell, Signal, Scaffold

“Biologics are here to stay & will be a mainstay of many operative & non-operative

treatment protocols.”- JPB, 2011

#10

Thank youPittsburgh Pa