Intramuscular osteoinduction and bone marrow formation by the implantation of rhBMP-2 with atelopeptide type I collagen

The incidence of ligament injury has recently been estimated at 400,000/year. The preferred treatment is reconstruction using an allograft, but outcomes are limited by donor availability, biomechanical incompatibility, and immune rejection. The creation of an engineered ligament in vitro solely from patient bone marrow stromal cells (has the potential to greatly enhance outcomes in knee reconstructions. Our laboratory has developed a scaffoldless method to engineer three-dimensional (3D) ligament and bone constructs from rat bone marrow stem cells in vitro. Coculture of these two engineered constructs results in a 3D bone-ligament-bone (BLB) construct with viable entheses, which was successfully used for medial collateral ligament (MCL) replacement in a rat model. 1 month and 2 month implantations were applied to the engineered BLBs. Implantation of 3D BLBs in a MCL replacement application demonstrated that our in vitro engineered tissues grew and remodeled quickly in vivo to an advanced phenotype and partially restored function of the knee. The explanted 3D BLB ligament region stained positively for type I collagen and elastin and was well vascularized after 1 and 2 months in vivo. Tangent moduli of the ligament portion of the 3D BLB 1 month explants increased by a factor of 2.4 over in vitro controls, to a value equivalent to those observed in 14-day-old neonatal rat MCLs. The 3D BLB 1 month explants also exhibited a functionally graded response that closely matched native MCL inhomogeneity, indicating the constructs functionally adapted in vivo.

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Promotion of Hepatic Differentiation of Bone Marrow Mesenchymal Stem Cells on Decellularized Cell-Deposited Extracellular Matrix

BioMed Research International ◽

10.1155/2013/406871 ◽

2013 ◽

Vol 2013 ◽

pp. 1-11 ◽

Cited By ~ 19

Author(s):

Hongliang He ◽

Xiaozhen Liu ◽

Liang Peng ◽

Zhiliang Gao ◽

Yun Ye ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Extracellular Matrix ◽

Mesenchymal Stem Cells ◽

Stem Cell ◽

Type I Collagen ◽

Type Iii Collagen ◽

Type I ◽

Hepatic Differentiation ◽

Marrow Mesenchymal Stem Cells

Interactions between stem cells and extracellular matrix (ECM) are requisite for inducing lineage-specific differentiation and maintaining biological functions of mesenchymal stem cells by providing a composite set of chemical and structural signals. Here we investigated if cell-deposited ECM mimickedin vivoliver's stem cell microenvironment and facilitated hepatogenic maturation. Decellularization process preserved the fibrillar microstructure and a mix of matrix proteins in cell-deposited ECM, such as type I collagen, type III collagen, fibronectin, and laminin that were identical to those found in native liver. Compared with the cells on tissue culture polystyrene (TCPS), bone marrow mesenchymal stem cells (BM-MSCs) cultured on cell-deposited ECM showed a spindle-like shape, a robust proliferative capacity, and a suppressed level of intracellular reactive oxygen species, accompanied with upregulation of two superoxide dismutases. Hepatocyte-like cells differentiated from BM-MSCs on ECM were determined with a more intensive staining of glycogen storage, an elevated level of urea biosynthesis, and higher expressions of hepatocyte-specific genes in contrast to those on TCPS. These results demonstrate that cell-deposited ECM can be an effective method to facilitate hepatic maturation of BM-MSCs and promote stem-cell-based liver regenerative medicine.

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Discoidin domain receptor 2 is involved in the activation of bone marrow-derived dendritic cells caused by type I collagen

Biochemical and Biophysical Research Communications ◽

10.1016/j.bbrc.2006.11.010 ◽

2007 ◽

Vol 352 (1) ◽

pp. 244-250 ◽

Cited By ~ 27

Author(s):

Ji-Eun Lee ◽

Chon-Sik Kang ◽

Xiu-Ying Guan ◽

Beom-Tae Kim ◽

Sang-Hyun Kim ◽

...

Keyword(s):

Bone Marrow ◽

Dendritic Cells ◽

Type I Collagen ◽

Type I ◽

Discoidin Domain Receptor ◽

Discoidin Domain Receptor 2

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Influence of Deacetylated Chitin 50-TYPE I Collagen Complex Gel to Bone Marrow-Derived Mesenchymal Cells

Nihon Hotetsu Shika Gakkai Zasshi ◽

10.2186/jjps.50.542 ◽

2006 ◽

Vol 50 (4) ◽

pp. 542-551

Author(s):

Hideaki Kato ◽

Katsutoshi Wakabayashi ◽

Huminori Iwasa ◽

Tadaharu Kawawa ◽

Tetsuhiko Tachikawa

Keyword(s):

Bone Marrow ◽

Type I Collagen ◽

Mesenchymal Cells ◽

Type I

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Effect of Phosphatase and Tensin Homolog 12 on Osteogenic Differentiation of Bone Marrow Mesenchymal Stem Cells During Aging by Regulating Transforming Growth Factor Beta/Smad Signaling Pathway

Journal of Biomaterials and Tissue Engineering ◽

10.1166/jbt.2021.2723 ◽

2021 ◽

Vol 11 (8) ◽

pp. 1630-1635

Author(s):

Bin Wu ◽

Fenghua Bai ◽

Jianping Lin ◽

Guangji Wang ◽

Wentao Cai ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Cell Proliferation ◽

Osteogenic Differentiation ◽

Type I Collagen ◽

Type I ◽

Smad Signaling ◽

Alp Activity ◽

Smad Signaling Pathway ◽

Marrow Mesenchymal Stem Cells

Aging affects bone marrow mesenchymal stem cells (BMSC) differentiation. PTEN12 regulates cell proliferation and apoptosis. However, whether PTEN12 affects BMSCs osteogenic differentiation during aging is unknown. Two BMSCs derived from Zempster24−/− (senescence) and Zempster24+/+ (normal) mice were cultured in vitro. Real-time PCR analysis was used to analyze PTEN12 expression. PTEN12 siRNA was transfected into senescent Zempster24-/-BMSCs and after 14 days of osteogenic induction, cell proliferation was analyzed by MTT method along with measuring expression of osteocalcin, type I collagen, RUNX2 and OPN by Real time PCR, ALP activity, and TGFβ/smad signaling protein expression by Western blot. Compared to normal BMSCs, PTEN12 level in aging BMSCs was significantly elevated, osteocalcin, type I collagen, RUNX2 and OPN mRNA level was decreased along with reduced ALP activity and TGFβ1 and Smad2 expression (P < 0.05). PTEN12 siRNA transfection into senescent BMSCs significantly down-regulated PTEN12, upregulated osteocalcin, type I collagen, RUNX2 and OPN mRNA, increased ALP activity and TGFβ1 and Smad2 expression (P <0.05). Aging increases PTEN12 level and inhibits BMSCs osteogenic differentiation. Down-regulation of PTEN12 in BMSCs during aging can promote BMSCs osteogenic differentiation by regulating TGFβ/smad signaling pathway.

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Effects of Amelogenin on Proliferation, Differentiation, and Mineralization of Rat Bone Marrow Mesenchymal Stem CellsIn Vitro

The Scientific World JOURNAL ◽

10.1100/2012/879731 ◽

2012 ◽

Vol 2012 ◽

pp. 1-8 ◽

Cited By ~ 8

Author(s):

Masanobu Izumikawa ◽

Keijiro Hayashi ◽

Mohammad Ali Akbor Polan ◽

Jia Tang ◽

Takashi Saito

Keyword(s):

Bone Marrow ◽

Mrna Expression ◽

Type I Collagen ◽

Early Stage ◽

Enamel Matrix Derivative ◽

Major Protein ◽

Type I ◽

Rt Pcr ◽

Regenerative Therapies ◽

Rat Bone

The aim of this study was to clarify the function of amelogenin, the major protein of enamel matrix derivative, on the proliferation, differentiation, and mineralization of cultured rat bone marrow stem cells (BMSCs), toward the establishment of future bone regenerative therapies. No differences in the morphology of BMSCs or in cell numbers were found between amelogenin addition and additive-free groups. The promotion of ALPase activity and the formation of mineralized nodules were detected at an early stage in amelogenin addition group. In quantitative real-time RT-PCR, mRNA expression of osteopontin, osteonectin, and type I collagen was promoted for 0.5 hours and 24 hours by addition of amelogenin. The mRNA expression of osteocalcin and DMP-1 was also stimulated for 24 hours and 0.5 hours, respectively, in amelogenin addition group. These findings clearly indicate that amelogenin promoted the differentiation and mineralization of rat BMSCs but did not affect cell proliferation or cell morphology.

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Effects of Oral Anticoagulant Therapy on Gene Expression in Crosstalk between Osteogenic Progenitor Cells and Endothelial Cells

Journal of Clinical Medicine ◽

10.3390/jcm8030329 ◽

2019 ◽

Vol 8 (3) ◽

pp. 329 ◽

Cited By ~ 2

Author(s):

Luca Dalle Carbonare ◽

Monica Mottes ◽

Anna Brunelli ◽

Michela Deiana ◽

Samuele Cheri ◽

...

Keyword(s):

Gene Expression ◽

Bone Marrow ◽

Endothelial Cells ◽

Anticoagulant Therapy ◽

Type I Collagen ◽

Umbilical Vein ◽

Oral Anticoagulant Therapy ◽

Marker Gene ◽

Marker Genes ◽

Type I

Direct oral anti-coagulants (DOACs) are employed in clinical practice for the prevention and treatment of recurrent venous thromboembolism and for the prevention of stroke in non-valvular atrial fibrillation. DOACs directly and reversibly inhibit activated factor X or thrombin and can interfere with other pathophysiological processes such as inflammation, lipid metabolism, and bone turnover. We aimed to evaluate the possible effects of DOACs on osteogenesis and angiogenesis. We treated 34 patients affected by cardiovascular disorders with DOACs; biochemical and molecular analyses were performed before and after three months of treatment. Circulating progenitors (CPs; CD34−, CD45−, CD14−, CD73+, CD105+), which share typical bone marrow stem cell (MSCs) features, were harvested from peripheral blood of the study subjects to monitor the expression of osteogenesis-related genes RUNX2 and SPARC. Human umbilical vein endothelial cells (HUVECs) were used to probe angiogenesis-related VEGF, CD31, and CD105 gene expression. We performed co-culture experiments using a commercial human mesenchymal stem cells line (hMSCs) obtained from bone marrow and HUVECs. Clinical parameters related to bone metabolism, coagulation, renal and liver function, and the lipid profile were evaluated. Values of the C-terminal telopeptide type I collagen (CTX) increased after the treatment. We found a significant increase in osteogenesis marker gene expression in CPs after three months of anticoagulant therapy. An increase in the RUNX2 expression determinant alone was detected instead in hMSCs co-cultured with HUVECs in the presence of treated patients’ sera. The VEGF, CD31, and CD105 marker genes appeared to be significantly upregulated in HUVECs co-cultured with hMSCs in the presence of treated patients’ sera. Under these conditions, new vessel formation increased as well. Our results highlight an unexpected influence of DOAC therapy on osteogenic commitment and vascular endothelial function promotion.

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Introduction of a Mixture of β-Tricalcium Phosphate Into a Complex of Bone Marrow Mesenchymal Stem Cells and Type I Collagen Can Augment the Volume of Alveolar Bone Without Impairing Cementum Regeneration

Journal of Periodontology ◽

10.1902/jop.2014.140384 ◽

2015 ◽

Vol 86 (3) ◽

pp. 456-464 ◽

Cited By ~ 17

Author(s):

Takayosi Nagahara ◽

Shinichiro Yoshimatsu ◽

Hideki Shiba ◽

Hiroyuki Kawaguchi ◽

Katsuhiro Takeda ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Tricalcium Phosphate ◽

Type I Collagen ◽

Alveolar Bone ◽

Type I ◽

Marrow Mesenchymal Stem Cells

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MT1-MMP controls human mesenchymal stem cell trafficking and differentiation

Blood ◽

10.1182/blood-2009-06-228494 ◽

2010 ◽

Vol 115 (2) ◽

pp. 221-229 ◽

Cited By ~ 69

Author(s):

Changlian Lu ◽

Xiao-Yan Li ◽

Yuexian Hu ◽

R. Grant Rowe ◽

Stephen J. Weiss

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Molecular Mechanisms ◽

Type I Collagen ◽

Human Mesenchymal Stem Cells ◽

Human Mesenchymal Stem Cell ◽

Type I ◽

Cell Trafficking ◽

3 Dimensional ◽

Stem Cell Trafficking

Abstract Human mesenchymal stem cells (hMSCs) localized to bone marrow, nonhematopoietic organs, as well as perivascular niches are postulated to traffic through type I collagen-rich stromal tissues to first infiltrate sites of tissue damage, inflammation, or neoplasia and then differentiate. Nevertheless, the molecular mechanisms supporting the ability of hMSCs to remodel 3-dimensional (3D) collagenous barriers during trafficking or differentiation remain undefined. Herein, we demonstrate that hMSCs degrade and penetrate type I collagen networks in tandem with the expression of a 5-member set of collagenolytic matrix metalloproteinases (MMPs). Specific silencing of each of these proteases reveals that only a single membrane-tethered metalloenzyme, termed MT1-MMP, plays a required role in hMSC-mediated collagenolysis, 3D invasion, and intravasation. Further, once confined within type I collagen-rich tissue, MT1-MMP also controls hMSC differentiation in a 3D-specific fashion. Together, these data demonstrate that hMSC invasion and differentiation programs fall under the control of the pericellular collagenase, MT1-MMP.

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Hyaluronan-dependent motility of B cells and leukemic plasma cells in blood, but not of bone marrow plasma cells, in multiple myeloma: alternate use of receptor for hyaluronan-mediated motility (RHAMM) and CD44

Blood ◽

10.1182/blood.v87.5.1891.bloodjournal8751891 ◽

1996 ◽

Vol 87 (5) ◽

pp. 1891-1899 ◽

Cited By ~ 5

Author(s):

A Masellis-Smith ◽

AR Belch ◽

MJ Mant ◽

EA Turley ◽

LM Pilarski

Keyword(s):

Multiple Myeloma ◽

Bone Marrow ◽

B Cells ◽

Type I Collagen ◽

Collagen Type ◽

Plasma Cells ◽

Ex Vivo ◽

Time Lapse ◽

Collagen Type Iv ◽

Type I

We investigated the ability of blood B cells, bone marrow (BM) plasma cells, and terminal leukemic plasma cells (T-PCL) from patients with multiple myeloma (MM) to migrate on extracellular matrix proteins. Hyaluronan (HA), but not collagen type I, collagen type IV, or laminin, promoted migration of MM blood B cells, as determined by time-lapse video microscopy. Between 13% and 20% of MM blood B cells migrated on HA with an average velocity of 19 micron/min, and greater than 75% of MM blood B cells exhibited vigorous cell movement and plasma membrane deformation, as did circulating T-PCL and extraskeletal plasma cells from patients with MM. In contrast, plasma cells obtained from BM of patients with MM lacked motility on all substrates tested and did not exhibit cell membrane protrusions or cellular deformation. MM blood B cells and MM plasma cells from all sources examined expressed the HA- binding receptors receptor for HA-mediated motility (RHAMM) and CD44. On circulating MM B cells, both RHAMM and CD44 participated in HA- binding, indicating their expression ex vivo in an activated conformation. In contrast, for the majority of BM plasma cells in the majority of patients with MM, expression of RHAMM or CD44 was not accompanied by HA binding. A minority of patients did have HA-binding BM plasma cells, involving both RHAMM and CD44, as evidenced by partial blocking with monoclonal antibodies (MoAbs) to RHAMM or to CD44. Despite HA binding by both RHAMM and CD44, migration of MM blood B cells on HA was inhibited by anti-RHAMM but not by anti-CD44 MoAbs, indicating that RHAMM but not CD44 mediates motility on HA. Thus, circulating B and plasma cells in MM exhibit RHAMM- and HA-dependent motile behavior indicative of migratory potential, while BM plasma cells are sessile. We speculate that a subset(s) of circulating B or plasma cells mediates malignant spread in myeloma.

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