Matrix‐mediated retention of in vitro osteogenic differentiation potential and in vivo bone‐forming capacity by human adult bone marrow‐derived mesenchymal stem cells during ex vivo expansion

Abstract

Mesenchymal stem cells (MSCs) represent an attractive cell source for tissue engineering applications, since they are readily isolated from adult bone marrow and have the ability to differentiate along multiple mesenchymal lineages, including osteogenic. Currently, utilization of MSCs for bone tissue engineering is limited because of the attenuation of their osteogenic differentiation potential and in vivo bone-forming capacity following ex vivo expansion on conventional tissue culture plastic (TCP). Previously, we demonstrated that a denatured type I collagen (DC) matrix promotes the maintenance of MSC in vitro osteogenic differentiation potential during ex vivo expansion in contrast to TCP. In this study, we further demonstrate that the maintenance of MSC osteogenic differentiation potential is primarily due to the ability of DC matrix to influence the retention of early passage osteogenic functions in late passage (LP) cells during ex vivo expansion, in contrast to solely enhancing attenuated LP cellular functions during osteogenic differentiation. Serum-associated factors played a significant role in influencing the retention of MSC osteogenic differentiation potential during expansion on the DC matrix. Significantly, the results show that although LP cells expanded ex vivo on TCP highly attentuate their in vivo bone-forming capacity, the expansion of MSCs on DC matrix preserves this ability as determined by histological, histomorphometric, and bone mineral density evaluations of MSC-seeded hydroxyapatite/tricalcium phosphate scaffolds following an 8-week implantation period within a heterotopic muscle pouch model. These findings provide further insight into the importance of matrix-mediated effects on MSC function and selective factors important in this process.

Bone Regeneration Potential of Stem Cells Derived from Periodontal Ligament or Gingival Tissue Sources Encapsulated in RGD-Modified Alginate Scaffold

“…41,44,45 We demonstrate here that MSCs derived from orofacial tissues show promise as a therapeutic option and do not suffer from the drawbacks of the current bone regeneration techniques. 42,43,46 From a practical perspective, gingival tissues (and to some extent the periodontal ligaments) provide superior sources of MSCs considering their accessibility and ready availability for autologous transplantation.…”

“…[36][37][38] RGD-coupled alginate scaffolds therefore provide a favorable physiochemical microenvironment by presenting ligands that specifically bind to cell receptors. [38][39][40][41] However, a literature search revealed no reports that assess the bone regenerative capacity of encapsulated PDLSCs and GMSCs in RGD-coupled alginate microspheres. Indeed, overall in comparison to other dentalderived MSCs, these two easily accessible stem cell sources have not been studied widely.…”

Incidence of bone formation by whole bone marrow cell suspensions and by its stromal cell cultures injected into kidney parenchyma of Balb/c mice

“…Expansion of MSC on conventional tissue culture plastic attenuates in vitro osteogenic differentiation and in vivo osteogenesis. To maintain osteogenic differentiation potential, the MSC should be propagated on collagen matrix [10].…”

Non-invasive characterization of structure and morphology of silk fibroin biomaterials using non-linear microscopy

“…cellular proliferation [1,5], differentiation [6][7][8], deposition of new structural proteins [9,10] and ultimately the regeneration of functional tissue [4,11,12]. Traditionally, methods such as NMR, FTIR and X-Ray spectroscopy have been used to assess biomaterials at the molecular level [13][14][15][16][17], while SEM and TEM have been invaluable tools for characterizing the three dimensional morphology of biomaterial scaffolds [5,[18][19][20][21][22][23].…”