Autologous Mesenchymal Stroma Cells Are Superior to Allogeneic Ones in Bone Defect Regeneration

The application of autologous mesenchymal stem cells (MSC) for the treatment of bone defects requires two invasive procedures and several weeks of ex vivo cell expansion. To overcome these limitations, the administration of allogeneic MSC may be attractive, because they are anticipated to be immunoprivileged. Because preclinical studies using various animal models are conflicting with respect to the efficacy of allogeneic MSC, we investigated whether autologous and allogeneic human MSC (hMSC) are equally effective in regenerating bone in a humanized mouse model resembling the human immune system. Applying autologous and allogeneic hMSC in critically sized femoral defects, we found that allogeneic hMSC elicited a mild immune response early after implantation, whereas early angiogenic processes were similar in both treatments. At later healing time points, the transplantation of allogeneic hMSC resulted in less bone formation than autologous hMSC, associated with a reduced expression of the osteogenic factor Runx2 and impaired angiogenesis. We found by species-specific staining for collagen-type-1α2 that MSCs of either source did not synthesize new bone matrix, indicating an indirect contribution of transplanted hMSC to bone regeneration. In conclusion, our data suggest that the application of autologous hMSC is superior to that of allogeneic cells for bone defect treatment.

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XMODULATION IN MICEAND MEN: IL-10 PRODUCING CELLS INBLOOD AND LYMPHOID TISSUE

Clinical & Investigative Medicine ◽

10.25011/cim.v31i4.4789 ◽

2008 ◽

Vol 31 (4) ◽

pp. 3

Author(s):

L Barrett ◽

M Grant ◽

R Liwski ◽

K West

Keyword(s):

Immune System ◽

Peripheral Blood ◽

Lymphoid Tissue ◽

Mononuclear Cells ◽

Ex Vivo ◽

White Blood Cells ◽

Interleukin 10 ◽

Healthy Individuals ◽

Human Immune System ◽

Healthy Humans

Background: The human immune system provides remarkable protection from a plethora of pathogens, but can cause damage when activated for a prolonged time (as inpersistent infections) or against self (autoimmunity). Therefore, mechanisms of immune system downregulation and control are imperative. There is little data on how the immune system is controlled in healthy individuals. We recently described a novel population of white blood cells that constitutively produce the immunomodulatory cytokine interleukin-10 (IL-10). Our objective was to further delineate the distribution of these cells in human and mouse models, as well as potential triggers for interleukin-10 production in vitro. Methods: Human and animal protocols were reviewed and approved by the institutional ethics board and animal care facilities, and informed consent was obtained from all human donors. The ex vivo percentage of peripheral blood CD36^+IL-10^+ mononuclear cells was assessed by intracellular flow cytometry in 10 healthy individuals. IL-10 production after exposure to twoCD36 ligands, thrombospondin and oxidized low density lipoprotein (oxLDL) was measured at 8 hours. Peripheral blood mononuclear cells and splenocytes from BL/6 (n=5) and Balb/c (n=1) micewere assessed for CD36^+IL-10^+ cells ex vivo as well. Results: The percentage of CD36^+IL-10^+ cells in peripheral blood fromhealthy individuals ranges between 0.1% and 0.9%. The percentage was similar in mouse peripheral blood, with a range of 0.4%-1.1%. These cells were also found in mouse spleen at a higher frequency than peripherally (1.1-1.5%). Human CD36^+IL-10^+ cells have more IL-10 when exposed to thrombospondin, oxLDL. Conclusions: Our novel population of IL-10 producing cells is found not only in healthy humans, but also in lymphoid tissue and blood from pathogen free mice. This highlights the evolutionary conservation of the cell across species, and suggests an important homeostatic function. The physiologic ligands for CD36 are ubiquitous in circulation, and ourin vitro data suggests a link between CD36 ligation and IL-10 production. IL-10 is a known immune system modulator, and its production by these cells may help maintain homeostaticcontrol of the immune system.

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Impaired Alignment of Bone Matrix Microstructure Associated with Disorganized Osteoblast Arrangement in Malignant Melanoma Metastasis

Biomolecules ◽

10.3390/biom11020131 ◽

2021 ◽

Vol 11 (2) ◽

pp. 131

Author(s):

Aira Matsugaki ◽

Yumi Kimura ◽

Ryota Watanabe ◽

Fumihito Nakamura ◽

Ryo Takehana ◽

...

Keyword(s):

Malignant Melanoma ◽

Cell Activation ◽

Ex Vivo ◽

Bone Matrix ◽

Melanoma Metastasis ◽

Mineral Density ◽

High Fracture ◽

Matrix Microstructure ◽

Metastasis Model

Malignant melanoma favors spreading to bone, resulting in a weakened bone with a high fracture risk. Here, we revealed the disorganized alignment of apatite crystals in the bone matrix associated with the homing of cancer cells by developing an artificially controlled ex vivo melanoma bone metastasis model. The ex vivo metastasis model reflects the progressive melanoma cell activation in vivo, resulting in decreased bone mineral density and expression of MMP1-positive cells. Moreover, less organized intercellular connections were observed in the neighboring osteoblasts in metastasized bone, indicating the abnormal and randomized organization of bone matrix secreted by disconnected osteoblasts. Our study revealed that the deteriorated microstructure associated with disorganized osteoblast arrangement was a determinant of malignant melanoma-related bone dysfunction.

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Three-dimensional-printed individualized porous implants: A new “implant-bone” interface fusion concept for large bone defect treatment

Bioactive Materials ◽

10.1016/j.bioactmat.2021.03.030 ◽

2021 ◽

Vol 6 (11) ◽

pp. 3659-3670

Author(s):

Teng Zhang ◽

Qingguang Wei ◽

Hua Zhou ◽

Zehao Jing ◽

Xiaoguang Liu ◽

...

Keyword(s):

Bone Defect ◽

Three Dimensional ◽

Large Bone Defect ◽

Bone Interface ◽

Fusion Concept ◽

Bone Defect Treatment ◽

Large Bone

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A pilot study: Alternative biomaterials in critical sized bone defect treatment

Injury ◽

10.1016/j.injury.2017.11.007 ◽

2018 ◽

Vol 49 (3) ◽

pp. 523-531 ◽

Cited By ~ 10

Author(s):

Magdalena Tarchala ◽

Victor Engel ◽

Jake Barralet ◽

Edward J. Harvey

Keyword(s):

Pilot Study ◽

Bone Defect ◽

Bone Defect Treatment

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Experimental bone defect healing with xenogenic demineralized bone matrix and bovine fetal growth plate as a new xenograft: radiological, histopathological and biomechanical evaluation

Cell and Tissue Banking ◽

10.1007/s10561-008-9107-y ◽

2008 ◽

Vol 10 (1) ◽

pp. 33-41 ◽

Cited By ~ 14

Author(s):

A. S. Bigham ◽

S. N. Dehghani ◽

Z. Shafiei ◽

S. Torabi Nezhad

Keyword(s):

Growth Plate ◽

Bone Defect ◽

Fetal Growth ◽

Demineralized Bone Matrix ◽

Bone Matrix ◽

Defect Healing ◽

Bone Defect Healing ◽

Biomechanical Evaluation ◽

Demineralized Bone

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Role of the autologous mesenchymal stem cells compared with platelet rich plasma on cicatrization of cutaneous wounds in diabetic mice

Pesquisa Veterinária Brasileira ◽

10.1590/s0100-736x2016000700010 ◽

2016 ◽

Vol 36 (7) ◽

pp. 617-624

Author(s):

Napoleão M. Argolo Neto ◽

Ricardo J. Del Carlo ◽

Betânia S. Monteiro ◽

Nance B. Nardi ◽

Pedro C. Chagastelles ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Platelet Rich Plasma ◽

Cutaneous Lesion ◽

Healing Time ◽

Diabetic Mice ◽

Cutaneous Lesions ◽

Cutaneous Wounds ◽

Autologous Mesenchymal Stem Cells ◽

Treatment Of Wounds

Abstract: Chronic cutaneous lesions affect 15% of diabetic human patients and represent a risk 15 to 46 times larger of limb amputations compared to people with normal glycemia. It is assumed that half of these amputations could be prevented by early treatment of wounds, for example, with proper cell therapy. Objectives: In this study, the action of the autologous transplant of mesenchymal stem-cells (MSC) was evaluated compared to the treatment with autologous platelet rich plasma (PRP) in the cicatrization of cutaneous lesions induced in diabetic mice. These animals were previously treated with streptozootocin to induce diabetes mellitus and round wounds of 1.5cm in diameter were created in the posterior region. Diameters of the wounds and healing time were evaluated during 30 days and the results were submitted to variance analysis and Tukey's test average. It was noticed that the animals treated with MSC presented a more accelerated cicatrization of the cutaneous lesion than the animals treated with PRP. However, the treatment with PRP presented better results than just the daily asepsis of the lesions with saline or covering them with semi-permeable bandage. Besides, the use of semi-permeable bandage kept the cutaneous lesions of diabetic mice did not interfere negatively with cicatrization, proved to be harmless to use, but kept the cutaneous lesions more hydrated than the ones exposed to the environment.

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P06.07 In vivo studies of immunomodulatory a-CTLA-4 antibody in a humanized mouse model

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2021-itoc8.41 ◽

2021 ◽

Vol 9 (Suppl 1) ◽

pp. A22.1-A22

Author(s):

C Reitinger ◽

F Nimmerjahn

Keyword(s):

Immune System ◽

Mouse Model ◽

Cancer Immunotherapy ◽

Model Systems ◽

Checkpoint Control ◽

Human Immune System ◽

Humanized Mouse ◽

Humanized Mouse Model ◽

Human Immune

BackgroundRecent findings in cancer immunotherapy have reinforced the hypothesis that the immune system is able to control most cancers. Immunomodulatory antibodies can enhance immune responses, having the potential to generate anti-cancer immunity.1–4Materials and MethodsMost current studies addressing this question are performed in murine mouse model systems or use in vitro culture systems, which do not reflect the human in vivo situation, potentially leading to results that cannot be fully translated into human cancer therapy. Therefore, it is necessary to establish a new mouse model, which allows the study of cancer immunotherapy in the context of a human immune system. We focused on the establishment of a humanized mouse model, in which different immunomodulatory antibodies can be tested in the presence of a human immune system.ResultsFirst experiments concerning the suitability to test immunomodulatory antibodies in the humanized mouse model, revealed that effects of checkpoint-control antibody a-CTLA-4 were similar to the effects seen in patients of clinical studies. To analyse the anti-tumor activities of immunomodulatory antibodies in vivo we are establishing a human melanoma-like tumor model in humanized mice.ConclusionsThis enables us to test the efficacy of immunomodulatory agonistic antibodies (such as CP-870,893) and checkpoint control antibodies (such as anti-CTLA-4) in eliminating a melanoma-like tumor. Furthermore, parameters like tumor infiltrating human cells und cytokine/chemokine production can be analysed.ReferencesSchuster M, Nechansky A, Loibner H. Cancer immunotherapy. Biotechnol J 2006;1:138–147.Mellman I, Coukos G, Dranoff G. Cancer immunotherapy comes of age. Nature rev 2011;480:480–489.Finn OJ. Immuno-oncology: understanding the function and dysfunction of the immune system in cancer. Annals of Oncology 2012;23:vii6–vii9.Langer LF, Clay TM, Morse MA. Update on anti-CTLA-4 in clinical trials. Expert Opin Biol Ther 2007;8:1245–1256.Disclosure InformationC. Reitinger: None. F. Nimmerjahn: None.

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Histopathological and Radiographical Evaluation of Caprine Demineralized Bone Matrix in a Critical Ulnar Defect in a Rabbit Model

10.21203/rs.3.rs-853202/v1 ◽

2021 ◽

Author(s):

Olawale Alimi Alimi ◽

Adamu Abdul Abuabakar ◽

Abubakar Sadiq Yakubu ◽

Sani Abdullahi Shehu ◽

Salman Zubairu Abdulkadir

Keyword(s):

Bone Defect ◽

Demineralized Bone Matrix ◽

Bone Matrix ◽

Rabbit Model ◽

Negative Control ◽

Autogenous Bone ◽

Level Of Evidence ◽

Defect Sites ◽

Significant Difference ◽

Demineralized Bone

Abstract Background: Caprine species satisfy the conditions of an ideal donor animal when compared to bovine species that has been extensively studied and commercialized for bone xenograft. Histopathological and radiological evaluations of caprine demineralized bone matrix (CDBM) were therefore carried out for fracture healing properties for its possible use in bone grafting procedures. Materials and Methods: Twenty-four rabbits were used for this study and were divided randomly into three groups of eight (n=8) rabbits each. Critical bone defect was created on the ulnar diaphysis under xylazine-ketamine anaesthesia for autogenous bone graft (ABG) group, CDBM group and the last group was left unfilled as negative control (NC). Immediate post-grafting radiograph was taken and repeated on days 14, 28, 42 and 56 to monitor the evidence of radiographic healing. The animals were euthanized on day 56 and defect sites were harvested for histopathology. Results: There was a progressive evidence of radiographic healing and bone formation in all the groups with significance difference (P=0.0064). When compared with ABG, NC differ significantly (P<0.0001) whereas the CDBM did not differ significantly (P=0.6765). The histopathology sections of ABG and CDBM showed normal bone tissue while the NC section was predominated by fibrous connective tissue. There was therefore an overall significant difference (P=0.0001) in which CDBM did not differ from ABG (P=0.2946) while NC did (P=0.0005). Conclusion: The ABG and CDBM groups showed a similar healing effect in the critical bone defect. Therefore, CDBM could be used as an effective alternative to ABG in orthopaedics to circumvent the limitations and complications associated with it. Level of Evidence: Not applicable.

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