scholarly journals Age Does Matter: A Pilot Comparison of Placenta-Derived Stromal Cells for in utero Repair of Myelomeningocele Using a Lamb Model

2015 ◽  
Vol 39 (3) ◽  
pp. 179-185 ◽  
Author(s):  
Erin G. Brown ◽  
Benjamin A. Keller ◽  
Lee Lankford ◽  
Christopher D. Pivetti ◽  
Shinjiro Hirose ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Motor Function ◽  
Stromal Cells ◽  
In Utero ◽  
Skin Closure ◽  
Sheep Model ◽  
Fetal Sheep ◽  
Early Gestation ◽  
Large Neurons

Introduction: Fetal amniotic membranes (FM) have been shown to preserve spinal cord histology in the fetal sheep model of myelomeningocele (MMC). This study compares the effectiveness of placenta-derived mesenchymal stromal cells (PMSCs) from early-gestation versus term-gestation placenta to augment FM repair to improve distal motor function in a sheep model. Methods: Fetal lambs (n = 4) underwent surgical MMC creation followed by repair with FM patch with term-gestation PMSCs (n = 1), FM with early-gestation PMSCs (n = 1), FM only (n = 1), and skin closure only (n = 1). Histopathology and motor assessment was performed. Results: Histopathologic analysis demonstrated increased preservation of spinal cord architecture and large neurons in the lamb repaired with early-gestation cells compared to all others. Lambs repaired with skin closure only, FM alone, and term-gestation PMSCs exhibited extremely limited distal motor function; the lamb repaired with early-gestation PMSCs was capable of normal ambulation. Discussion: This pilot study is the first in vivo comparison of different gestational-age placenta-derived stromal cells for repair in the fetal sheep MMC model. The preservation of large neurons and markedly improved motor function in the lamb repaired with early-gestation cells suggest that early-gestation placental stromal cells may exhibit unique properties that augment in utero MMC repair to improve paralysis.

scholarly journals CD34+ human marrow cells that express low levels of Kit protein are enriched for long-term marrow-engrafting cells

Blood ◽  
1996 ◽  
Vol 87 (10) ◽  
pp. 4136-4142 ◽  
Author(s):  
I Kawashima ◽  
ED Zanjani ◽  
G Almaida-Porada ◽  
AW Flake ◽  
H Zeng ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Cells ◽  
Marrow Cell ◽  
In Utero ◽  
Fetal Sheep ◽  
Hematopoietic Stem ◽  
Show Evidence ◽  
Marrow Cells

Using in utero transplantation into fetal sheep, we examined the capability of human bone marrow CD34+ cells fractionated based on Kit protein expression to provide long-term in vivo engraftment. Twelve hundred to 5,000 CD34+ Kit-, CD34+ Kit(low), and CD34+ Kit(high) cells were injected into a total of 14 preimmune fetal sheep recipients using the amniotic bubble technique. Six fetuses were killed in utero 1.5 months after bone marrow cell transplantation. Two fetuses receiving CD34+ Kit(low) cells showed signs of engraftment according to analysis of CD45+ cells in their bone marrow cells and karyotype studies of the colonies grown in methylcellulose culture. In contrast, two fetuses receiving CD34+ Kit(high) cells and two fetuses receiving CD34+ Kit- cells failed to show evidence of significant engraftment. Two fetuses were absorbed. A total of six fetuses receiving different cell populations were allowed to proceed to term, and the newborn sheep were serially examined for the presence of chimerism. Again, only the two sheep receiving CD34+ Kit(low) cells exhibited signs of engraftment upon serial examination. Earlier in studies of murine hematopoiesis, we have shown stage-specific changes in Kit expression by the progenitors. The studies of human cells reported here are in agreement with observations in mice, and indicate that human hematopoietic stem cells are enriched in the Kit(low) population.

Hard Tissue Augmentation of Aged Bone by Means of a Tin-Free PLLA-PCL Co-Polymer Exhibiting in vivo Anergy and Long-Term Structural Stability

Gerontology ◽  
2019 ◽  
Vol 65 (2) ◽  
pp. 174-185 ◽  
Author(s):  
Magdalena M. Schimke ◽  
Swaraj Paul ◽  
Katharina Tillmann ◽  
Günter Lepperdinger ◽  
Robert G. Stigler
Keyword(s):  
Stromal Cells ◽  
Perfusion Culture ◽  
Autologous Bone Marrow ◽  
Porous Scaffolds ◽  
Sheep Model ◽  
Physicochemical Stability ◽  
Space Filler ◽  
Post Implantation

Background: Due to aging, tissue regeneration gradually declines. Contemporary strategies to promote tissue-specific regeneration, in particular in elderly patients, often include synthetic material apt for implantation primarily aiming at upholding body functions and regaining appropriate anatomical and functional integrity. Objective: Biomaterials suitable for complex reconstruction surgical procedures have to exert high physicochemical stability and biocompatibility. Method: A polymer made of poly-L-lactic acid and poly-ε-caprolactone was synthesized by means of a novel tin-free catalytic process. The material was tested in a bioreactor-assisted perfusion culture and implanted in a sheep model for lateral augmentation of the mandible. Histological and volumetric evaluation was performed 3 and 6 months post-implantation. Results: After synthesis the material could be further refined by cryogrinding and sintering, thus yielding differently porous scaffolds that exhibited a firm and stable appearance. In perfusion culture, no disintegration was observed for extended periods of up to 7 weeks, while mesenchymal stromal cells readily attached to the material, steadily proliferated, and deposited extracellular calcium. The material was tested in vivo together with autologous bone marrow-derived stromal cells. Up to 6 months post-implantation, the material hardly changed in shape with composition also refraining from foreign body reactions. Conclusion: Given the long-term shape stability in vivo, featuring imperceptible degradation and little scarring as well as exerting good compatibility to cells and surrounding tissues, this novel biomaterial is suitable as a space filler in large anatomical defects.

Homing of Human Cells in the Fetal Sheep Model: Modulation by Antibodies Activating or Inhibiting Very Late Activation Antigen-4–Dependent Function

Blood ◽  
1999 ◽  
Vol 94 (7) ◽  
pp. 2515-2522 ◽  
Author(s):  
Esmail D. Zanjani ◽  
Alan W. Flake ◽  
Graça Almeida-Porada ◽  
Nam Tran ◽  
Thalia Papayannopoulou
Keyword(s):  
Molecular Mechanisms ◽  
Fetal Liver ◽  
In Utero ◽  
Human Cells ◽  
Human Donor ◽  
Sheep Model ◽  
Fetal Sheep ◽  
In Utero Transplantation ◽  
Donor Cells ◽  
Activation Antigen

The mechanisms by which intravenously (IV)-administered hematopoietic cells home to the bone marrow (BM) are poorly defined. Although insightful information has been obtained in mice, our knowledge about homing of human cells is very limited. In the present study, we investigated the importance of very late activation antigen (VLA)-4 in the early phases of lodgment of human CD34+progenitors into the sheep hematopoietic compartment after in utero transplantation. We have found that preincubation of donor cells with anti–VLA-4 blocking antibodies resulted in a profound reduction of human cell lodgment in the fetal BM at 24 and 48 hours after transplantation, with a corresponding increase of human cells in the peripheral circulation. Furthermore, IV infusion of the anti–VLA-4 antibody at later times (posttransplantation days 21 to 24) resulted in redistribution or mobilization of human progenitors from the BM to the peripheral blood. In an attempt to positively modulate homing, we also pretreated human donor cells with an activating antibody to β1 integrins. This treatment resulted in increased lodgment of donor cells in the fetal liver, presumably for hemodynamic reasons, at the expense of the BM. Given previous involvement of the VLA-4/vascular cell adhesion molecule (VCAM)-1 adhesion pathway in homing and mobilization in the murine system, our present data suggest that cross-reacting ligands (likely VCAM-1) for human VLA-4 exist in sheep BM, thereby implicating conservation of molecular mechanisms of homing and mobilization across disparate species barriers. Thus, information from xenogeneic models of human hematopoiesis and specifically, the human/sheep model of in utero transplantation, may provide valuable insights into human hematopoietic transplantation biology.

Cotransplantation of human stromal cell progenitors into preimmune fetal sheep results in early appearance of human donor cells in circulation and boosts cell levels in bone marrow at later time points after transplantation

Blood ◽  
2000 ◽  
Vol 95 (11) ◽  
pp. 3620-3627 ◽  
Author(s):  
Graça Almeida-Porada ◽  
Christopher D. Porada ◽  
Nam Tran ◽  
Esmail D. Zanjani
Keyword(s):  
Bone Marrow ◽  
Stromal Cells ◽  
Stromal Cell ◽  
In Utero ◽  
Human Cells ◽  
Fetal Sheep ◽  
Hematopoietic Stem ◽  
Donor Cells ◽  
Hsc Transplantation

Both in utero and postnatal hematopoietic stem cell (HSC) transplantation would benefit from the development of approaches that produce increased levels of engraftment or a reduction in the period of time required for reconstitution. We used the in utero model of human–sheep HSC transplantation to investigate ways of improving engraftment and differentiation of donor cells after transplantation. We hypothesized that providing a more suitable microenvironment in the form of human stromal cell progenitors simultaneously with the transplanted human HSC would result in higher rates of engraftment or differentiation of the human cells in this xenogeneic model. The results presented here demonstrate that the cotransplantation of both autologous and allogeneic human bone marrow-derived stromal cell progenitors resulted in an enhancement of long-term engraftment of human cells in the bone marrow of the chimeric animals and in earlier and higher levels of donor cells in circulation both during gestation and after birth. By using marked stromal cells, we have also demonstrated that injected stromal cells alone engraft and remain functional within the sheep hematopoietic microenvironment. Application of this method to clinical HSC transplantation could potentially lead to increased levels of long-term engraftment, a reduction in the time for hematopoietic reconstitution, and a means of delivery of foreign genes to the hematopoietic system.

scholarly journals Effect of Shikonin on Spinal Cord Injury in Rats Via Regulation of HMGB1/TLR4/NF-kB Signaling Pathway

2017 ◽  
Vol 43 (2) ◽  
pp. 481-491 ◽  
Author(s):  
Yihui Bi ◽  
Yapeng Zhu ◽  
Mingkai Zhang ◽  
Keke Zhang ◽  
Xingyi Hua ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Inflammatory Response ◽  
Signaling Pathway ◽  
Motor Function ◽  
Tissue Repair ◽  
Underlying Mechanism ◽  
Molecular Signaling ◽  
Cord Injury

Background/Aims: Shikonin, a compound extracted from Zicao, has been demonstrated to hold anti-bacterial, anti-inflammatory, and anti-tumor activities in various diseases and it has been shown to protect human organs from injuries. However, the effect of shikonin on the recovery of spinal cord injury (SCI) remains unknown. This study was designed to estimate the potential therapeutic effect and underlying mechanism of shikonin on SCI in vivo. Methods: In the study, we used HE staining, ELISA assay, transfection assay, TUNEL assay, real time PCR and Western blot to detect the effects of shikonin on spinal cord injury in rats. Results: we showed that shikonin could promote the recovery of motor function and tissue repair after SCI treatment in rats SCI model. Moreover, we demonstrated that shikonin inhibited the spinal cord edema in SCI model of rats. According to further investigation, shikonin induced the reduction of inflammatory response through decreasing the expression levels of HMGB1, TLR4 and NF-κB after SCI injury. In addition, we also found that shikonin could suppress the apoptosis and expression of caspase-3 protein in SCI model of rats. Conclusion: Our results demonstrated that shikonin induced the recovery of tissue repair and motor function via inactivation of HMGB1/TLR4/NF-κB signaling pathway in SCI model of rats. Meanwhile, shikonin regulated the inflammation response in SCI by suppressing the HMGB1/TLR4/NF-κB signaling pathway. The described mechanism sheds novel light on molecular signaling pathway in spinal cord injury and secondary injury including inflammatory response.

scholarly journals Ultrasonographic Development of the Fetal Sheep Stomach and Evaluation of Early Gestation Ultrasound-guided In Utero Intragastric Injection

2010 ◽  
Vol 49 (1) ◽  
pp. 23-29 ◽  
Author(s):  
Anna L. David ◽  
Khalil N. Abi-Nader ◽  
Boaz Weisz ◽  
S.W. Steven Shaw ◽  
Michael Themis ◽  
...  
Keyword(s):  
In Utero ◽  
Ultrasound Guided ◽  
Fetal Sheep ◽  
Early Gestation

scholarly journals Pericyte-derived fibrotic scarring is conserved across diverse central nervous system lesions

2020 ◽  
Author(s):  
David O. Dias ◽  
Jannis Kalkitsas ◽  
Yildiz Kelahmetoglu ◽  
Cynthia P. Estrada ◽  
Jemal Tatarishvili ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Nervous System ◽  
Mouse Models ◽  
Stromal Cells ◽  
Primary Source ◽  
Lineage Tracing ◽  
Fibrotic Tissue ◽  
Cord Injury

AbstractFibrotic scar tissue limits central nervous system regeneration in adult mammals. The extent of fibrotic tissue generation and distribution of stromal cells across different lesions in the brain and spinal cord has not been systematically investigated in mice and humans. Furthermore, it is unknown whether scar-forming stromal cells have the same origin throughout the central nervous system and in different types of lesions. In the current study, we compared fibrotic scarring in human pathological tissue and corresponding mouse models of penetrating and non-penetrating spinal cord injury, traumatic brain injury, ischemic stroke, multiple sclerosis and glioblastoma. We show that the extent and distribution of stromal cells are specific to the type of lesion and, in most cases, similar between mice and humans. Employing in vivo lineage tracing, we report that in all mouse models developing fibrotic tissue, the primary source of scar-forming fibroblasts is a discrete subset of perivascular cells, termed type A pericytes.We uncover pericyte-derived fibrosis as a conserved mechanism that may be explored as a therapeutic target to improve recovery after central nervous system lesions.

scholarly journals High density placental mesenchymal stromal cells provide neuronal preservation and improve motor function following in utero treatment of ovine myelomeningocele

2019 ◽  
Vol 54 (1) ◽  
pp. 75-79 ◽  
Author(s):  
Melissa Vanover ◽  
Christopher Pivetti ◽  
Lee Lankford ◽  
Priyadarsini Kumar ◽  
Laura Galganski ◽  
...  
Keyword(s):  
Motor Function ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
In Utero ◽  
High Density ◽  
Improve Motor Function
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