Impaired Bone Healing due to Dysfunctional Stem Cells

$194
Raised of $6,485 Goal
3%
Ended on 3/11/15
Campaign Ended
  • $194
    pledged
  • 3%
    funded
  • Finished
    on 3/11/15

About This Project

We study a special group of Stem Cells that reside in the Bone Marrow called mesenchymal stem cells (MSC). We believe that the MSC are deficient in patients with a failing hip or knee implant. We hope that a close examination of these stem cells will allow us to develop therapies that could prolong the life of a failing implant.

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What is the context of this research?

The failing implant has a very high chance of fracturing. In 2015, we anticipate that nearly 1,250,000 patients will get either a new knee or hip implant while 125,000 patients are going to require a revision surgery for a failing hip or knee implant. By 2030, however, nearly 4 million patients will need either a hip or knee implant while approximately 300,000 patients will require a revision of a failing total joint implant. Revision total joint surgeries have been observed to have a lower rate of overall success when compared to primary total joint surgeries, which is attributed to a less robust bone quality that leads to poor bone-implant integration.


Our recent work shows that MSC from revision patients is no longer capable of efficient bone formation.

What is the significance of this project?

Our recent work represents the first time MSC have been examined in the niche surrounding a failed implant.

Importantly, our application of the PDGFRa/CD51 surface markers to identify MSC surrounding a failed total joint implant represents a novel and innovative approach to assessing the stem cell niche in patients with a failed implant.

We believe this knowledge will be critical for the development of drug therapies that will increase the longevity of existing joint implants that are in the process of failing or drug therapies/ biologic, cell based (MSC) therapies that increase the success in revision surgeries.

What are the goals of the project?

Our broad project goal is the determine is there are differences between healthy MSC versus MSC collected from a failing knee or hip implants.

1. Are the surface markers that we use to identify MSC (PDGFRa/ CD51) expressed equally in both healthy MSC and the MSC we have identified as deficient?

2. Are PDGFRa/CD51 MSC collected from next to a failing implant able to make bone cells as efficiently as PDGFRa/CD51 MSC from healthy bone marrow controls?

3. Do PDGFRa/ CD51 MSC collected from next to a failing implant express the same patterns of genes?

Budget

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We are seeking funding to determine if there are differences between the mesenchymal stem cells (MSC) collected from 3 patients with failing total joint implants versus 3 patients with healthy MSC. To measure these differences we must determine the numbers of MSC by examining a set of cell surface markers. Cell surface markers, however, cannot tell us anything about whether the MSC remain capable of normal function. To determine the functional capacity of the MSC, we will use gene expression and functional assays.

The markers that we need to employ to identify MSC are very expensive (7 antibodies for $279 per antibody) as are the reagents needed to analyze gene expression and to generate the MSC collected from patients.

Unfortunately, beginning this work has been hampered by the lack of funding available for this study through more traditional routes. The patients who will benefit from our research continue to have hip or knee implants that fail, without the benefit of new treatments.



Meet the Team

Bryan S. Margulies
Bryan S. Margulies

Team Bio

I became interested in mesenchymal stem cell (MSC) biology and the potential therapeutic application of MSC through my collaborations with an orthopedic total joint surgeon and an orthopedic spine surgeon. Repairing total joint implants that have failed or spine fusions that have failed are significant clinical proble



My Non-Science Life: My partner and I have been together for almost 10-years and we are very involved with our respective families. We are both active runners and enjoy competing in local 5K races. I have lived in central New York for 18-years. We both love the Adirondacks and visit at least once a year. I have kept aquarium fish since 7-years of age, with two tanks (1 x in my office and 1x at home) stocked with African rift lake cichlids. I am also an avid reader, when time permits (I have been reading the fantasy novels of Terry Pratchett, recently).

Bryan S. Margulies

My Research: Bones self-regulate their pattern and shape during growth. This process is remarkable when you consider that bone adapts to a changing mechanical environment shaped by an individual's level of activity throughout their entire life. We understand that part of this process is mediated by bone stem cells known as mesenchymal stem cells (MSC) and signaling proteins that govern the process through which MSC choose to become a bone cell. However, it is unknown how MSC decide where to migrate and under what circumstances do they choose to become a bone cell and start making new bone. We believe that developing an understanding of how MSC migrate and then differentiate into a bone cell are critical to treating the following bone diseases: First, treatment for childhood bone cancers (sarcoma) often leads to bone that does not heal and can fracture easily. We believe that both of these problems are due to the failure of MSC to migrate into the sites of surgical intervention and then re-start the process of normal bone turn-over (i.e. destruction followed by formation). Second, failure of total hip or knee implants leads to significant health complications in older adults and is on the cusp of being a public health crisis. Implant failure is thought to be due to poor integration of the metal implant with the surrounding bone; a process that we have shown is dependent on having healthy MSC next to the implant.

My Non-Science Life: My partner and I have been together for almost 10-years and we are very involved with our respective families. We are both active runners and enjoy competing in local 5K races. I have lived in central New York for 18-years. We both love the Adirondacks and visit at least once a year. I have kept aquarium fish since 7-years of age, with two tanks (1 x in my office and 1x at home) stocked with African rift lake cichlids. I am also an avid reader, when time permits (I have been reading the fantasy novels of Terry Pratchett, recently).

Press and Media

  • Margulies BS, DeBoyace SD, Parsons AM, Policastro CG, Ee JSS, Damron TA. (2014) Functionally Deficient Mesenchymal Stem Cells Reside in the Bone Marrow Niche with M2-macrophages and Amyloid-β Protein Adjacent to Loose Total Joint Implants. J Orthop Res. 2014 Nov 22. doi: 10.1002/jor.22790. [Epub ahead of print]

Project Backers

  • 6Backers
  • 3%Funded
  • $194Total Donations
  • $32.33Average Donation
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