Why Bone Marrow-Derived Stem Cells?

Bone marrow-derived stem cells are used for a variety of conditions in large and small animals including the following:

Equine

Meniscal Lesions
Tendon & Ligament Injuries
Degenerative Osteoarthritis (OA)
OA secondary to Osteochondrosis

Canine

Meniscal Lesions
Tendon & Ligament Injuries
Degenerative Osteoarthritis (OA)
OA secondary to Osteochondrosis
Bone healing/Osteotomy sites

Bone marrow-derived mesenchymal stem cells are the best characterized population of stem cells currently under consideration for applications in regenerative medicine (Smith, 2008). In laboratory studies BMMSC’s have demonstrated the ability to differentiate into bone, cartilage, tendon, ligament, meniscus, intervertebral disc, fat, muscle, and nerve cells (Muschler et al,2004).

When compared in laboratory studies, BMMSC’s clearly outperformed adipose-derived mesenchymal stem cells in models of cartilage (Winter et al, 2003; Im et al, 2005; Kisiday et al, 2008; Noel et al, 2008; Vidal et al, 2008) and bone differentiation (Im et al 2005; Noel et al 2008).

In laboratory studies [Bone Marrow-Derived Stem Cells] have demonstrated the ability to differentiate into bone, cartilage, tendon, ligament, meniscus, intervertebral disc, fat, muscle, and nerve cells.

Culture expansion of BMMSC’s for clinical applications yields highly homogenous populations of stem cells numbering in the tens of millions. Estimated yields for adipose-derived practices in which culture expansion is not conducted are in the hundreds of thousands (Frisbie and Smith, 2010).

Multicenter long term clinical follow-up data is available for bone marrow derived therapies (Ferris et al, 2009; Godwin et al, 2011).

The following has been reported for treatment of superficial digital flexor tendon (SDFT) injuries with BMMSC’s:

A. The rates of reinjury were significantly reduced 72%, (n=71)) vs. 46% (n=208) in BMMSC treated National Hunt Horses after two years relative to standard SDFT tendinopathy treatment methods (Dyson, 2004; Fortier and Smith; 2008; Godwin et al, 2011).

B. In a 2007 study following racehorses that were treated for SDFT injuries, those that received conventional therapy had a reinjury rate of 100% within 12 months (n=15). Horses treated with BMMSC’s had a reinjury rate of only 18% (n=11) in the same time frame. Of the 9 horses that received BMMSC’s and returned to racing, all had improved ultrasound images at 6 months and produced good to optimal racing performances within one year (Pacini et al, 2007).

A randomized, blinded, placebo controlled study on intra-articular administration of expanded stem cells in a goat total medial meniscectomy model demonstrated Regeneration of menisci in 7/9 cases (Murphy et al 2003).

A prospective multicenter trial on bone marrow derived stem cell administrations in horses followed for an average of 21 months showed the following (Ferris et al 2009):

  • 85% treated for tendon or ligament injuries returned to work (n=61). 51% returned to or exceeded their previous level of work without the need for additional treatment. 34% returned to work but at a lesser level.
  • 76% treated via intrasynovial administration returned to work. (n=39). 38% returned or exceeded their prior level of work. 38% returned to work, but at a lesser level

Study on SDFT re-injury rates in national hunt horses treated without stem cells showed 56% re-injured within 24 months (Dyson 2004).

A second study of SDFT injured horses treated with marrow derived stem cells reported only 24% reinjured (Fortier, Smith 2008)

An Italian study in racehorses showed that 9 out of 11 stem cell treated animals were back to racing with good to optimal results at 12 months. (Pacini et al 2007)

Of control horses, 100% had re-injured over the same time period.

Applications of Bone Marrow-Derived Stem Cells

Bone marrow-derived stem cells are used for a variety of conditions in large and small animals including the following:

Equine

  • Meniscal Lesions
  • Tendon/Ligament injuries
  • Degenerative Osteoarthritis (OA)
  • OA secondary to Osteochondrosis

Canine

  • Meniscal Lesions
  • Tendon/Ligament injuries
  • Degenerative Osteoarthritis (OA)
  • OA secondary to Osteochondrosis
  • Bone healing/Osteotomy sites

References

Smith, R.K. (2008) Mesenchymal stem cell therapy for equine tendinopathy. Disabil. Rehabil. 30, 1752-1758.

Muschler, G.F., Nakamoto, C., Griffith, L.G. (2004) Engineering principles of clinical cell-based tissue engineering. J. Bone Joint Surg. Am. 86-A, 1541-1558.

Winter, A., Breit, S., Parsch, D., Benz, K., Steck, E., Hauner, H., Weber, R.M., Ewerbeck, V., Richter, W. (2003) Cartilage-like gene expression in differentiated human stem cell spheroids: a comparison of bone marrow- derived and adipose tissue-derived stromal cells. Arthritis Rheum. 48, 418-429.

Im, G.I., Shin, Y.W., Lee, K.B. (2005) Do adipose tissue-derived mesenchymal stem cells have the same osteogenic and chondrogenic potential as bone marrow derived cells? Osteoarthritis Cartilage 13, 845-853.

Kisiday, J.D., Kopesky, P.W., Evans, C.H., Grodzinsky, A.J., McIlwraith, C.W., Frisbie, D.D. (2008) Evaluation of adult equine bone marrow- and adipose derived progenitor cell chondrogenesis in hydrogel cultures. J. Orthop. Res. 26,322-331.

Noel, D., Caton, D., Roche, S., Bony, C., Lehmann, S., Casteilla, L., Jorgensen, C., Cousin, B. (2008) Cell specific differences between human adipose-derived and mesenchymal-stromal cells despite similar differentiation potentials. Expt. Cell Res. 314, 1575-1584.

Vidal, M.A., Robinson, S.O., Lopez, M.J., Paulsen, D.B., Borkhsenious, O., Johnson, J.R., Moore, R.M., Gimble, J.M. (2008) Comparison of chondrogenic potential in equine mesenchymal stromal cells derived from adipose tissue and bone marrow. Vet. Surg. 37, 713-724.

Frisbie, D.D., Smith, R.K. (2010) Clinical update on the use of mesenchymal stem cells in equine orthopaedics Equine Vet. J. 42 (1), 86-89.

Ferris, D.J., Frisbie, D.D., Kisiday, J.D., McIlwraith, C.W., Hague, B.A., Major,M.D., Schneider, R.K., Zubrod, C.J., Watkins, J.J., Kawcak, C.E., Goodrich, L.R. (2009) Clinical follow-up of horses treated with bone marrow derived mesenchymal stem cells for musculoskeletal lesions. Proc. Am. Ass. Equine Practnrs. 55, 59-60.

Godwin, E.E., Young, N.J., Dudhia, J., Beamish, I.C., Smith, R.K. (2011) Implantation of bone marrow-derived mesenchymal stem cells demonstates improved ooutcome in horses with overstrain injury of the superficial digital flexor tendon. Equine Vet. J. doi: 10.111/j.2042-3306.2011.00363. x.

Fortier, L.A. and Smith, R.K. (2008) Regenerative medicine for tendinous and ligamentous injuries of sport horses. Vet. Clin. N. Am.: Equine Pract. 24, 191-201.

Dyson, S.J. (2004) Medical management of superficial digital flexor tendonitis: a comparative study in 219 horses (1992-2000). Equine Vet. J. 36, 415-419.

Pacini, S., Spinabella, S., Trombi, L., Fazzi, R., Galimberti, S., Dini, F., Carlucci, F., Petrini, M. (2007) Suspension of bone marrow-derived undifferentiated mesenchymal stromal cells for repair of superficial digital flexor tendon in racehorses. Tissue Eng. 13, 2949-2955.