Multipotent adult progenitor cells on an allograft scaffold facilitate the bone repair process

Abstract

Multipotent adult progenitor cells are a recently described population of stem cells derived from the bone marrow stroma. Research has demonstrated the potential of multipotent adult progenitor cells for treating ischemic injury and cardiovascular repair; however, understanding of multipotent adult progenitor cells in orthopedic applications remains limited. In this study, we evaluate the osteogenic and angiogenic capacity of multipotent adult progenitor cells, both in vitro and loaded onto demineralized bone matrix in vivo, with comparison to mesenchymal stem cells, as the current standard. When compared to mesenchymal stem cells, multipotent adult progenitor cells exhibited a more robust angiogenic protein release profile in vitro and developed more extensive vasculature within 2 weeks in vivo. The establishment of this vascular network is critical to the ossification process, as it allows nutrient exchange and provides an influx of osteoprogenitor cells to the wound site. In vitro assays confirmed the multipotency of multipotent adult progenitor cells along mesodermal lineages and demonstrated the enhanced expression of alkaline phosphatase and production of calcium-containing mineral deposits by multipotent adult progenitor cells, necessary precursors for osteogenesis. In combination with a demineralized bone matrix scaffold, multipotent adult progenitor cells demonstrated enhanced revascularization and new bone formation in vivo in an orthotopic defect model when compared to mesenchymal stem cells on demineralized bone matrix or demineralized bone matrix–only control groups. The potent combination of angiogenic and osteogenic properties provided by multipotent adult progenitor cells appears to create a synergistic amplification of the bone healing process. Our results indicate that multipotent adult progenitor cells have the potential to better promote tissue regeneration and healing and to be a functional cell source for use in orthopedic applications.

A comparison of radiographic and clinical outcomes of anterior lumbar interbody fusion performed with either a cellular bone allograft containing multipotent adult progenitor cells or recombinant human bone morphogenetic protein-2

“…While bone morphogenetic proteins have been recognized as stimulating osteogenesis and increasing osteoblastic activity, there is still a need for blood vessels to support the new bone tissue [ 22 ]. In vitro testing has demonstrated the ability of MAPC-based cells to secrete vascular endothelial growth factor (VEGF), CXCL-5, and interleukin-8, all of which are important in stimulating angiogenesis [ 23 ].…”

Alginate encapsulated multipotent adult progenitor cells promote corneal stromal cell activation via release of soluble factors

“…Starting with exploring the effect of XFM media on MAPC cultures phenotype, MAPC thawed from liquid nitrogen seeded in a 2000 cells/cm 2 density and grown and maintained in XFM medium for 72 hours at 37°C were analyzed for morphology, proliferation, and viability. Phase-contrast micrographs showed that cells acquired their typical small, spindle-shaped, fibroblastic-like morphology [ 33 , 34 ]. This shape persisted over three days in culture as was previously shown [ 28 ] ( Fig 2A ).…”

“…MAPC have previously been shown to have promising therapeutic immunoregulatory effects driven ostensibly by their ability to produce paracrine effector molecules [ 35 ]. As such the secretory behavior of these cells has successfully shown to be influential in the treatment of a variety of clinical conditions, such as hind limb ischemia [ 36 ], multiple sclerosis [ 37 ], myelodysplastic syndrome [ 16 ], acute ischemic stroke [ 11 ], and bone repair [ 33 ]. However, unlike MSCs, MAPC have not yet been tested in vitro on corneal stromal cell growth.…”

Plasma‐Activated Substrate with a Tropoelastin Anchor for the Maintenance and Delivery of Multipotent Adult Progenitor Cells

“…Delivered MAPCs are expected to accelerate wound healing and to improve the quality of newly formed tissue via a multipronged approach. These cells can modulate the immune response to resolve inflammation; differentiate into skin progenitor cells, attract fibroblasts and keratinocytes, and stimulate ECM production for wound closure and dermal regeneration; secrete proangiogenic factors (e.g., CXCL5) and differentiate into endothelial cells for neovasculature formation; and recruit other endogenous stem cells that participate in wound healing . The paracrine effects of cytokines and growth factors secreted by MAPCs also suggest a way by which undelivered cells tethered on the functionalized patch can confer supplementary healing benefits, to augment those of delivered cells which often have short residence time in the wound site.…”

“…They are nonimmunogenic, can be administered without tissue matching, survive in the hypoxic wound environment that typically inhibits healing, and possess broad differentiation potential into mesodermal, endodermal, and neuroectodermal cell types . MAPCs have been shown to improve tissue regeneration in a number of disease models such as myocardial infarction, ischemia, and brain, spinal cord, and bone injuries . Like MSCs, MAPCs secrete immunomodulatory, pro‐proliferative, and angiogenic factors important for wound healing.…”