Enhancing Bone Healing with Mesenchymal Stem Cells

The ability for bone to naturally repair fractures and other common injuries have been well documented.  However, research has consistently demonstrated that as they age,  bone loses its ability to heal, repair, and fend off various bone diseases. In fact, each year, in the U.S. alone, there are over 2 million fragility-associated fractures with associated healthcare costs exceeding more than $20 billion dollars.

Currently, non-stem cell bone healing therapies including estrogen and related agonists, recombinant parathyroid hormone, supplements such as vitamin D and calcium exist, but with limitations and a number of potentially serious side effects.

Considering that the incidence of fracture and the associate rate of morbidity increase with age, current research is now examining other therapeutic options for the structural and functional restoration of bone, including the viability and of tissue engineering applications such as mesenchymal stem cells (MSCs) and bioscaffolding as potential solutions for the structural and functional restoration of bone.

Stem cells are generally used therapeutically in three distinct ways, including 1.) freshly isolated stem cells transplanted directly into tissue and undergo in vivo differentiation to become a desired cell type; 2.) the stem cell can be manipulated in vitro prior to being implanted; or 3.) circulating endogenous stem cells are recruited by cytokines to facilitate cell proliferation, migration, adhesion, and differentiation.

As researchers continue to explore using MSCs as part of therapeutic bone regeneration, it is generally accepted that MSC bone marrow density and quality decrease with age.  In addition, a factor in determining the effectiveness of MSCs related to facilitating tissue repair is the ability for the stem cells to be directed to the site of injury, a process more commonly known as “homing”.  A recent study using mice has demonstrated that MSCs appear to lose their homing ability rapidly while young MSCs demonstrate better homing ability, especially when compared to old MSCs.  Considering this, future research must consider the age of both donor and recipient when determining the effectiveness of this strategy.

In addition to stem cells, bioscaffolds are also considered an essential component of the bone regeneration strategy, serving as the reservoir for multiple factors, the carrier for cells, the filler for the void space, and the template for bone regeneration.  The ideal scaffold for bone tissue engineering has been identified as:

  • Showing no local and systemic toxic effects to the host tissue
  • Supporting normal cellular activity
  • Allowing cell adhesion, proliferation, extracellular matrix deposition, and inducting new bone formation
  • Prompting the formation of blood vessels after weeks of implantation.

Considering the above, several substrates have been identified as potential bioscaffolds to support improved regeneration of bone tissue, including decellularized extracellular matrix scaffolds, synthetic scaffolds (calcium phosphate-based bioactive ceramic scaffolds; metallic scaffolds (including metal scaffolds coated with growth factors and other bioactive factors); hybrid scaffolds combining two or more materials (metal-ceramic-poly hybrid scaffolds); natural and synthetic polymeric scaffolds; and nanomaterial-based scaffolds.

As research continues to explore the possibilities of new therapeutic approaches to bone healing provided through various tissue engineering applications, the use of MSCs and bioscaffolds continue to demonstrate potential benefits.  Among the key areas requiring further study is the need to develop vascularization in engineered bone material.  Bone and bone tissue has a rich vascular supply; while the recent study has demonstrated nanomaterials as having the potential to promote vascularization (without the aid of growth factors), further research and clinical trial are required.

Reference: (2018, June 22). Bone Marrow Mesenchymal Stem Cells: Aging … – NCBI – NIH. Retrieved December 18, 2020, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6733253/

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