This presentation communicates current methods for rotator cuff repair mainly focusing on mesenchymal and tendon-derived stem cells. It looks to expand on future research in this field by communicating a future experiment to expand on current knowledge of tendon-derived stem cells.

1. Rotator Cuff Repair Using a
Stem Cell Approach
By: Zakary Bondy

2. Outline
 Introduction
 Introduction to Stem Cells
 Bone Marrow-Derived Mesenchymal Stem Cells
 Animal Model 1
 Animal Model 2
 Clinical Trial 1
 Tendon-Derived Stem Cells and Past Studies
 Hypothesis
 Specific Aims
 Methods
 Conclusion

3. Introduction
Multiple muscles and tendons
Supraspinatus tendon being the major issue
2 million people in 2013 went to doctors
because of rotator cuff issues
30% of patients visit orthopaedic clinic
because of rotator cuff issues
Acute Tearing
Sports
Straining

4. Introduction Degenerative Tearing
Increasing amount of people experiencing
rotator cuff tears in their 50’s and 60’s
Due to impingement
Surgery on degenerative tears can be more
harmful

5. Stem Cells
Scar tissue forms after RC surgery
Increases likelihood of re-tear
Unspecialized cells, ability to proliferate
Tendon, bone, muscle, neurons- promote healing
This research is narrowed down to
1. Bone Marrow-Derived (BMD) Mesenchymal Stem
Cells (MSCs)
2. Tendon-Derived Stem Cells (TDSCs)

6. BMD Mesenchymal Stem Cells
Found to take part in local repair and regeneration of
bone, articular cartilage, intervertebral discs, and tendons
MSCs show healing on tendon grafts, but not known if
this can be applied to RCs
Can differentiate into osteoblasts, chondrocytes,
adipocytes, tenocytes, myotubes, neural cells, and more
either in vivo or in vitro

7. Animal Model 1
 Hypothesis: Tendon Attachment strength will increase
 10 Lewis rats used to retrieve MSCs from
 98 Lewis rats underwent acute supraspinatus tearing
 Tendon sutured back together
 Some rats received:
1. No implant
2. Injection of MSCs in a fibrin carrier
3. Only injection of fibrin carrier
 4 rats received MSCs transduced with Ad-LacZ to repair site
 Blue color emitted when LacZ interacts with substrate
 Rats sacrificed at weeks 2 and 4

8. Animal Model 1
Results:
Ad-LacZ injected MSCs
seen the figure to the
right
Put under uniaxial
testing
At 4 weeks, control and
MSC groups showed
the same ultimate
stress to failure
Hypothesis not
supported

9. Animal Model 2
 Hypothesis: That MSCs will survive after implantation in vivo
and will promote cellular differentiation in a scaffold
 50 male New Zealand White rabbits
7 to 10 mL bone marrow aspirated from iliac crest from each
rabbit
Centrifuged
Autologous
 Open-cell Polylactic acid (OPLA) 3D scaffold used
One RC had MSCs integrated into OPLA, other side had OPLA
used as a control
 PKH-26 used as fluorescent dye that transfers to daughter
cells of MSCs
 Rabbits euthanized at 2, 4, and 6 weeks

10. Animal Model 2
Results:
 Fluorescent staining
analysis at:
2 weeks
6 weeks
A – MSC integrated
B - control

11. Animal Model 2
Results:
 Immunohistochemical
analysis used to determine
type I
2, 4, and 6 weeks
MSC integrated (left)
Control (right)
 Collagen I expression
higher in MSC scaffold

12. Clinical Trial 1
Bone marrow aspirated from patient’s proximal
humerus – all obtained autologously
Platelet-poor plasma (PPP) as source of fibrinogen for
scaffold matrix
Platelet-rich plasma (PRP) used as source for growth
factors
Concentrated bone marrow aspirate (cBMA) used as
source of MSCs
Fibrin clot created to deliver MSC’s and growth
factors as a biological scaffold
Bovine thrombin used to retain a stable clot

13. Procedure
Two medial row
sutures fed through
lateral portal and
attached across the
tendon tear
Fibrin clot then
inserted it close to the
suture

14. Tendon-Derived Stem Cells and Past Studies
Discovered in 2007
Not until 2012 were they researched specifically for
rotator cuff tears
Some studies from the past few years showed the
following:
TSG-6 mediates the function of TDSCs to improve the
structure and attachment strength of the healing tendon-
to-bone interface
EGR1 induces TDSCs tenogenic differentiation and plays a
key role in tendon formation, healing, and repair
FGF-2 promotes growth of tenogenic progenitor cells,
promoting healing and biomechanical strength

15. Hypothesis
Hypothesis: Under similar conditions where MSCs
resulted in increased collagen I, TDSCs will also
increase in collagen I
In certain studies, MSCs have been shown to
introduce tumor induction or ectopic bone formation
Therefore, recommended MSCs differentiated prior to
cellular transplantation

16. Specific Aims:
1. Create a 3-dimensional open-cell scaffold for non-
autologous TDSCs
 Used to create a controlled living environment for
TDSCs
 Integrated as new supraspinatus tendon
2. Determine collagen I differences over a duration of
time
 Collagen I amounts will be compared with that of a
control at weeks 6, 8, and 12

17. Methods
 Inserting 60 OPLA scaffolds into each rabbits supraspinatus
tendon (biodegradable)
35 rabbits used in total, 5 used for aspiration of TDSCs
Rabbits have only a 1.4% anesthetic-related death rate
TDSCs are unable to be retrieved analogously
 Rabbits euthanized at 6, 8, and 12 weeks
Need enough time for TDSCs to integrate themselves into the
OPLA scaffold
Using immunostaining, collagen I formation and integration will
be determined

18. Conclusion
Current rotator cuff issues
Why stem cells would help in rotator cuff repair
Bone Marrow-Derived Mesenchymal Stem Cells and
where they lack
Tendon-Derived Stem Cells and Past Studies
Hypothesis, collagen I increase over time when
integrating TDSCs into an OPLA scaffold

19. References
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20. References
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 http://www.bonetalks.com/armrotatorcufftear/

21. Questions?