scholarly journals Biologic Characteristics of Bone Substituting Tissue Engineering Construction Based on Calcium Phosphate Ceramics, Autologous Mesenchymal Stromal Cells and Fibrin Hydrogel

Author(s):  
V. E. Mamonov ◽  
A. G. Chemis ◽  
V. S. Komlev ◽  
A. L. Berkovskiy ◽  
E. M. Golubev ◽  
...  

Biological characteristics of bone substituting tissue engineering construction (TEC) that contained porous calcium phosphate ceramic granulate (CPC) of phase structure ((tricalcium phosphate (TCP)), fibrin hydrogel and autologous multipotent mesenchymal stromal cells (auto-MMSC) induced and non-induced to osteogenic differentiation were studied in vivo. The following characteristics of TEC were determined: ability to transfer within its structure the viable auto-MMSC with preservation of their regeneration potential; ability to osteogenesis only under conditions of orthotopic implantation; ability of induced to osteogenic differentiation auto-MMSC to participate in the reparative processes for not more than within 6 weeks after implantation; negative affect of fibrin hydrogel on the osteoinductive properties of CPC within TCP structure. It was shown that to provide osteogenesis in the implanted TEC not only the viable auto-MMSC but simultaneous presence of osteoinductive and osteoconductive factors was required. No bone formation in a critical bone defect and in ectopic implantation takes place without observance of these conditions.

2015 ◽  
Vol 22 (4) ◽  
pp. 52-59
Author(s):  
V. E Mamonov ◽  
A. G Chemis ◽  
V. S Komlev ◽  
A. L Berkovskiy ◽  
E. M Golubev ◽  
...  

Biological characteristics of bone substituting tissue engineering construction (TEC) that contained porous calcium phosphate ceramic granulate (CPC) of phase structure ((tricalcium phosphate (TCP)), fibrin hydrogel and autologous multipotent mesenchymal stromal cells (auto-MMSC) induced and non-induced to osteogenic differentiation were studied in vivo. The following characteristics of TEC were determined: ability to transfer within its structure the viable auto-MMSC with preservation of their regeneration potential; ability to osteogenesis only under conditions of orthotopic implantation; ability of induced to osteogenic differentiation auto-MMSC to participate in the reparative processes for not more than within 6 weeks after implantation; negative affect of fibrin hydrogel on the osteoinductive properties of CPC within TCP structure. It was shown that to provide osteogenesis in the implanted TEC not only the viable auto-MMSC but simultaneous presence of osteoinductive and osteoconductive factors was required. No bone formation in a critical bone defect and in ectopic implantation takes place without observance of these conditions.


2019 ◽  
Vol 65 (4) ◽  
pp. 339-346
Author(s):  
L.S. Litvinova ◽  
V.V. Shupletsova ◽  
K.A. Yurova ◽  
O.G. Khaziakhmatova ◽  
N.M. Todosenko ◽  
...  

Secretion of 21 cytokines, chemokines and growth factors (LIF, SCF, SDF-1a, SCGF-b, M-CSF, MCP-3, MIF, MIG, TRAIL, GRO-a; IL-1a, IL-2ra, IL-3, IL-12(p40), IL-16, IL-18, HGF, TNF-b, b-NGF, IFN-a2, CTACK) has been studied in vitro in the culture of human adipose-derived multipotent mesenchymal stromal cells (hAMMSCs) in conditions of its osteogenic differentiation caused by 14-day contact with calcium phosphate (CP) surface with different roughness. Bilateral X-ray amorphous CP coatings were prepared on the samples of commercially pure titanium in the anodal regime using a micro-arc method. An aqueous solution prepared from 20 wt% phosphoric acid, 6 wt% dissolved hydrohyapatite nanopowder (particle diameter 10-30 nm with single agglomerates up to 100 nm), and 9 wt% dissolved calcium carbonate was used to obtain CP coating. hAMMSCs isolated from lipoaspirate were co-cultured after 4 passages with the CP-coated samples at final concentration of 1.5´105 viable karyocytes per 1.5 mL of standard nutrition medium (without osteogenic stimulators) for 14 days (a determination of [CD45,34,14,20], CD73, CD90 и CD105 cell immunophenotype; an analysis of secretory activity) and 21 days (alizarin red S staining of culture) with medium replacement every 3-4 days. Under conditions of in vitro contact with rough CP coating hAMMSCs differentiated into osteoblasts synthesizing the mineralized bone matrix; this was accompanied by 2-3-fold increasing ratio of [CD45,34,14,20]+ hemopoietic cells. The following humoral factors of hemopoietic niches acted as the signal molecules escalating in vitro the hemopoietic base in 14 days of differentiating three-dimensional culture of hAMMSCs: either leukemia inhibitory factor (LIF) and stem cell factor (SCF) cytokines under mean index of CP roughness Ra=2.4-2.6 mm or stromal derived factor-1 (SDF-1a, CXCL12 chemokine) under Ra=3.1-4.4 mm.


2004 ◽  
Vol 199 (3) ◽  
pp. 62
Author(s):  
Yun-Ying Shi ◽  
Randall Nacamuli ◽  
Ali Salim ◽  
Oliver Aalami ◽  
Catherine Cowan ◽  
...  

Cells ◽  
2019 ◽  
Vol 8 (5) ◽  
pp. 462 ◽  
Author(s):  
Luis A. Rodriguez ◽  
Arezoo Mohammadipoor ◽  
Lucero Alvarado ◽  
Robin M. Kamucheka ◽  
Amber M. Asher ◽  
...  

Multipotent mesenchymal stromal cells (MSCs) have emerged as potent therapeutic agents for multiple indications. However, recent evidence indicates that MSC function is compromised in the physiological post-injury milieu. In this study, bone marrow (BM)- and adipose-derived (AD)-MSCs were preconditioned in hypoxia with or without inflammatory mediators to potentiate their immunotherapeutic function in preparation for in vivo delivery. Human MSCs were cultured for 48 h in either normoxia (21% O2) or hypoxia (2% O2) with or without the addition of Cytomix, thus creating 4 groups: (1) normoxia (21%); (2) Cytomix-normoxia (+21%); (3) hypoxia (2%); and (4) Cytomix-hypoxia (+2%). The 4 MSC groups were subjected to comprehensive evaluation of their characteristics and function. Preconditioning did not alter common MSC surface markers; nonetheless, Cytomix treatment triggered an increase in tissue factor (TF) expression. Moreover, the BM-MSCs and AD-MSCs from the +2% group were not able to differentiate to chondrocytes and osteoblasts, respectively. Following Cytomix preconditioning, the metabolism of MSCs was significantly increased while viability was decreased in AD-MSCs, but not in BM-MSCs. MSCs from both tissues showed a significant upregulation of key anti-inflammatory genes, increased secretion of IL-1 receptor antagonist (RA), and enhanced suppression of T-cell proliferation following the Cytomix treatment. Similarly, following a lipopolysaccharide challenge, the Cytomix-treated MSCs suppressed TNF-α secretion, while promoting the production of IL-10 and IL-1RA. These preconditioning approaches facilitate the production of MSCs with robust anti-inflammatory properties. AD-MSCs preconditioned with Cytomix under normoxia appear to be the most promising therapeutic candidates; however, safety concerns, such as thrombogenic disposition of cells due to TF expression, should be carefully considered prior to clinical translation.


2017 ◽  
Vol 2017 ◽  
pp. 1-15 ◽  
Author(s):  
Per Anderson ◽  
Elena Gonzalez-Rey ◽  
Francisco O’Valle ◽  
Francisco Martin ◽  
F. Javier Oliver ◽  
...  

Multipotent mesenchymal stromal cells (MSCs) have emerged as a promising therapy for autoimmune diseases, including multiple sclerosis (MS). Administration of MSCs to MS patients has proven safe with signs of immunomodulation but their therapeutic efficacy remains low. The aim of the current study has been to further characterize the immunomodulatory mechanisms of adipose tissue-derived MSCs (ASCs) in vitro and in vivo using the EAE model of chronic brain inflammation in mice. We found that murine ASCs (mASCs) suppress T cell proliferation in vitro via inducible nitric oxide synthase (iNOS) and cyclooxygenase- (COX-) 1/2 activities. mASCs also prevented the lipopolysaccharide- (LPS-) induced maturation of dendritic cells (DCs) in vitro. The addition of the COX-1/2 inhibitor indomethacin, but not the iNOS inhibitor L-NAME, reversed the block in DC maturation implicating prostaglandin (PG) E2 in this process. In vivo, early administration of murine and human ASCs (hASCs) ameliorated myelin oligodendrocyte protein- (MOG35-55-) induced EAE in C57Bl/6 mice. Mechanistic studies showed that mASCs suppressed the function of autoantigen-specific T cells and also decreased the frequency of activated (CD11c+CD40high and CD11c+TNF-α+) DCs in draining lymph nodes (DLNs). In summary, these data suggest that mASCs reduce EAE severity, in part, through the impairment of DC and T cell function.


Sign in / Sign up

Export Citation Format

Share Document