4/15/2017 Bone&Joint

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Research: Further Opinion Leading research

and clinical practice
in orthopaedic

The use of the reamer-irrigator-

surgery
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aspirator to harvest mesenchymal

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G. Cox, D. McGonagle, S. A. Boxall, C. T. Buckley, E. Jones, P. V. Giannoudis best
musculoskeletal
J Bone Joint Surg [Br] 2011;93-B:517-24. science and
research
The authors have shown that the filtrate bag contained large numbers of mesenchymal stem cells that could be Current Issue
Archive
processed without needing cell expansion. RIA therefore provided a one-stage procedure to procure stem cells for
potential application to patients. No filtrate therefore should be discarded. They advocated using the concentrated
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stem cells together with the bone particles reamed (autografts) for the treatment of non-unions.
A global view in
In the current practice of stem cell application for musculoskeletal surgery, adult stem cells are preferred to embryonic orthopaedics
stem cells. The use of embryonic cells is surrounded by moral issues and also poses a risk of tumorigenesis.1In Current Issue
Archive
contrast, the use of adult stem cells from RIA is relatively free from such a risk.

Sources of autologous adult stem cells include iliac crest bone marrow aspirate and fat cells.2,3Stem cell
transplantation from these sources requires a two stage procedure. In the first stage the marrow is aspirated for Sign up to Table of Contents alerts
processing in the laboratory. The cells are isolated and then passaged several times to increase the number of cells to
the required 2 to 4 million cells needed for clinical transplantation.4Cells are usually used after two passages. This
processing takes about two weeks to complete in the laboratory. The transplantation of cells can only be done in a
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second stage after the first stage produces the cell pellet. It is pertinent to note that the passaging of cells can lead to
bizarre cell formation and apoptosis.5,6Since fresh cells could be obtained from RIA without the need for cell
expansion, these stem cells are less likely to develop bizarre cell formation and apoptosis a distinct advantage of RIA.

Stem cell applications in musculoskeletal surgery include cartilage, bone and tendon regeneration. RIA is unlikely to be
used as a source for cartilage regeneration since the bone particles or autologous bone grafts produced by the reaming
could not be used in tendon surgery. Discarding the bone particles cannot be justified. For the same reason, RIA cannot
be justified for procuring stem cells for tendon regeneration.

On the other hand, RIA could be useful for procuring bone particles and stem cells for bone regeneration whereby both
the stem cells and the bone particles could be used. It is a useful surgical technique for the production of tissue
engineered bone substitutes. The stem cells could be infiltrated into scaffolds such as hydroxyapatite blocks, tri-
calcium phosphate, coral or polycaprolactone-tricalcium phosphate blocks7to bridge large bone defects eg from
nonunions, surgery for tumour reconstruction or congenital pseudoathrosis of the tibia. Whilst one cannot insert bone
particles into the scaffold itself, the reamed bone autografts could be inserted into host-scaffold junctions to achieve
better union. RIA would be particularly useful when using allograft-stem cells constructs for the reconstruction of large
bone defects. Both stem cells and bone graft particles could be easily inserted into the medullary canal of the bone
allografts to achieve better biological incorporation of the allograft. They could also be inserted into both host-allograft
junctions to achieve union.8

RIA is particularly useful for bone applications such as the treatment of osteonecrosis of the hips,9,10for impaction
bone grafting in total hip replacement (Exeter Technique), for reconstruction of depressed articular fractures such as
lateral condylar fractures of the tibia, calcaneal fractures and fractures of the distal radius11. In spinal surgery, it could
be used to augment allografts by using autograft-allograft mixtures for posterior spinal fusion and for anterior spinal
reconstruction using femoral cortical ring allografts following corpectomt.12The addition of stem cells and bone
particles from RIA could increase the fusion rate in posterior spinal fusion and incorporate the ring allografts better in
anterior constructs. One could also explore infiltrating RIA cells and bone particles when performing kyphoplasty/
vertebroplasty procedures for osteoporotic wedge compression fractures of the spine. There are therefore several
applications of RIA for bone. However careful preliminary research is needed to evaluate the effectiveness of these
applications.

http://www.boneandjoint.org.uk/content/furtheropinion/usereamerirrigatoraspiratorharvestmesenchymalstemcells 1/2
4/15/2017 Bone&Joint
Whilst the authors have focused our attention on the presence of stem cells in the filtrate, they did not look into
another useful component of the filtrate namely the growth factors. In the production of Platelet Rich Plasma (PRP)
about 20ml of peripheral blood PRP Gel is produced by centrifugation. The gel contains local growth factors including
platelet derived growth factor and transforming growth factor (TGF).13The latter includes bone morphogenetic
proteins. In PRP production with centrifugation of peripheral blood, the junction of cells and serum the buffy coat is
the layer that is rich in growth factors. PRP gel is concentrated from this junction layer by a second spin. Likewise, in
the centrifugation of the RIA filtrate, the junction between stem cells and serum could also be rich in growth factors.
We could by a second spin similarly produce an RIA PRP gel. This would be another useful product that could be
obtained from the filtrate in addition to the cell pellet. More research needs to be done to look into the number of
growth factors that could be found in RIA PRP gel and also to evaluate their concentrations.

One can conclude that RIA is a good surgical technique that provides not only bone particles (autografts) but also
cells and growth factors. However, much more research needs to be done on the two products that could be
obtained from the RIA filtrate. Only then can the full potential of the usefulness of RIA technique be completely
realised.

References
1. Bongso A., Lee EH.Stem cells: from Bench to Bedside.World Scientific Publishing, 2005: 1-13.
2. Pittenger MF, Mackay AM, Beck SC, et al.Multilineage potential of adult human mesenchymal stem
cells.Science1999;284:143-7.
3. Muschler GF, Midura RJ.Connective Tissue Progenitors: Practical Concepts for Clinical Applications.Clin
Orthop2002;395:66-80.
4. Nather A, Das De S, Lee CW.Culturing mesenchymal stem cells from bone marrow. In Nather A (ed).Bone Grafts
and Bone Substitutes.World Scientific Publishing: New Jersey, London, Singapore. 2005:321-33.
5. Banfi A, Muraglia A, Dozin B, et al.Proliferation kinetics and differentiation potential of ex vivo expanded human
bone marrow stromal cells: Implications for their use in cell therapy.Exp Hematol2000;28:707-15.
6. Digirolamo CM, Stokes D, Colter D, et al.Propagation and senescence of human marrow stromal cells in culture: a
simple colony-forming assay identifies samples with the greatest potential to propagate and differentiate.Br J
Haematol1999;107:275-81.
7. Nather A, Aziz S.Scaffolds in Bone Tissue Engineering. In Nather A (ed).Bone Grafts and Bone Substitutes.World
Scientific Publishing: New Jersey, London, Singapore. 2005:357-66.
8. Nather A, David V, Teng JWH, Lee CW, Pereira BP.Effect of autologous mesenchymal stem cells on biological
healing of allografts in critical-sized defects simulated in adult rabbits.Ann Acad Med2010;39:599-606.
9. Gangji V, Hauzeur JP, Matos C, De Maetelaer V, Toungouz M, Lambermont M.Treatment of osteonecrosis of the
femoral head with implantation of autologous bone marrow cells. A pilot study.J Bone Joint Surg [Am]2004;86-
A:1153-60.
10. Hauzeur JP, Gangji V.Phases 1-3 clinical trials using adult stem cells in osteonecrosis and nonunion
fractures.Stem Cells Int2010;26;2010:410170.
11. Nather A, Khalid KA, Aziz Z.Clinical applications of gamma-irradiated deep-frozen and lyophilized bone
allografts The NUH Tissue Bank experience. In Nather A, Yusof N, Hilmy N (eds).Radiation in Tissue Banking,World
Scientific Publishing: New Jersey, London, Singapore. 2007. pp 305-315.
12. Nather A, Thambiah J.Allografts for Spinal Surgery. In Czitrom AA, Winkler H (eds).Orthopedic Allograft
Surgery.Springer: Wien, New York. 1996:203-210.
13. Das De S, Manohara R, Nather A.Platelet-Rich Plasma in Orthopaedic Surgery: Basic Sciences and Clinical
Applications. In Nather A (ed).Bone Grafts and Bone Substitutes.World Scientific Publishing: New Jersey, London,
Singapore. 2005:387-403.

Associate Professor Aziz Nather

Senior Consultant

Chairman, National University Hospital Diabetic Foot Team

Department of Orthopaedic Surgery

National University Hospital

1E, NUHS Tower Block, Level 11

Singapore 119228

Email:dosnathe@nus.edu.sg

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