Bone-Forming Capacity and Biodistribution of Bone Marrow-Derived Stromal Cells Directly Loaded into Scaffolds: A Novel and Easy Approach for Clinical Application of Bone Regeneration

Abstract

In the context of clinical applications of bone regeneration, cell seeding into scaffolds needs to be safe and easy. Moreover, cell density also plays a crucial role in the development of efficient bone tissue engineering constructs. The aim of this study was to develop and evaluate a simple and rapid cell seeding procedure on hydroxyapatite/ b-tricalcium phosphate (HA/bTCP), as well as define optimal cell density and control the biodistribution of grafted cells. To this end, human bone marrow-derived stromal cells (hBMSCs) were seeded on HA/bTCP scaffolds, and we have compared bone formation using an ectopic model. Our results demonstrated a significantly higher bone-forming capacity of hBMSCs directly loaded on HA/bTCP during surgery compared to hBMSCs preseeded for 7 days in vitro on HA/bTCP before ectopic implantation. The extent of new bone formation increases with increasing hBMSC densities quantitatively, qualitatively, and in frequency. Also, this study showed that grafted hBMSCs remained confined to the implantation site and did not spread toward other tissues, such as liver, spleen, lungs, heart, and kidneys. In conclusion, direct cell loading into a scaffold during surgery is more efficient for bone regeneration, as well as quick and safe. Therefore direct cell loading is suitable for clinical requirements and cell production control, making it a promising approach for orthopedic applications. Moreover, our results have provided evidence that the formation of a mature bone organ containing hematopoietic islets needs a sufficiently high local density of grafted hBMSCs, which should guide the optimal dose of cells for clinical use.

Stem Cell Therapy for the Treatment of Hip Osteonecrosis: A 30-Year Review of Progress

“…In a classical approach, bone tissue engineering consists of harvesting bone marrow from a patient, isolating MSCs by their adherence to tissue culture plastic, expanding and differentiating those cells in culture to a sufficient number and then seeding them onto a suitable synthetic scaffold prior to implantation into the same patient. 38 39 40 41) The autologous approach to isolation and osteogenic differentiation of MSCs is however highly demanding in terms of logistics, production and safety of culture conditions, leading to a costly therapeutic procedure. The association of biomaterials and osteoprogenitor cells raises technical challenges (i.e., cell sources, types, doses, and timing) and regulatory issues (devices with medicinal drugs) for the implementation of clinical trials.…”

Co‐transplantation of Wharton's jelly mesenchymal stem cell‐derived osteoblasts with differentiated endothelial cells does not stimulate blood vessel and osteoid formation in nude mice models

“…This density does not seem to be a limiting factor. Indeed, the best results in several similar studies were obtained on granules with densities ranging from 90,000 to 125,000 cells per milligram (Léotot et al, ; Mankani, Kuznetsov, Fowler, Kingman, & Robey, ; Mebarki et al, ). It should be noted, however, that the presence or absence of vessels was not assessed in these studies.…”

“…New bone formation (osteoids) was analysed on H&E stained sections. The relative surface area occupied by osteoids (%) was quantified on 15 sections (regardless of the implantation site because the results were the same for both subcutaneous and intramuscular implants) for each condition (empty scaffold; scaffold seeded with WJMSC‐OBs; scaffold seeded with WJMSC‐OBs + ECs), using ImageJ software (National Institutes of Health), as described previously by Léotot et al (). The total implant area was selected, and osteoid area was calculated as a percentage of the total area.…”

The Femoral Head of Patients with Hip Dysplasia is not as Osteogenic as Iliac Crest Bone Location

“…Careful pathologic assessments of retrieved grafts in humans have shown that the primary mode of union is via external host-derived callus which bridges the host-graft interface and leads to cortical -cortical and cancellous -cancellous bone union [25,26,11,19]. There is a gradual process of creeping replacement which works inward from the hostgraft junction toward the middle of the graft at a gradual rate [27][28][29][30].…”