scholarly journals Transforming the spleen into a liver-like organ in vivo

2020 ◽  
Vol 6 (24) ◽  
pp. eaaz9974
Author(s):  
Lintao Wang ◽  
Chunming Wang ◽  
Zhenzhen Wang ◽  
Jingjing Gan ◽  
Chunyan Liu ◽  
...  
Keyword(s):  
Tissue Regeneration ◽  
Liver Cells ◽  
The Body ◽  
Tissue Structure ◽  
Clinical Use ◽  
Immune Rejection ◽  
Severe Liver ◽  
Human Organs ◽  
Tumor Extract

Regenerating human organs remains an unmet medical challenge. Suitable transplants are scarce, while engineered tissues have a long way to go toward clinical use. Here, we demonstrate a different strategy that successfully transformed an existing, functionally dispensable organ to regenerate another functionally vital one in the body. Specifically, we injected a tumor extract into the mouse spleen to remodel its tissue structure into an immunosuppressive and proregenerative microenvironment. We implanted autologous, allogeneic, or xenogeneic liver cells (either primary or immortalized), which survived and proliferated in the remodeled spleen, without exerting adverse responses. Notably, the allografted primary liver cells exerted typical hepatic functions to rescue the host mice from severe liver damages including 90% hepatectomy. Our approach shows its competence in overcoming the key challenges in tissue regeneration, including insufficient transplants, immune rejection, and poor vascularization. It may be ready for translation into new therapies to regenerate large, complex human tissue/organs.

scholarly journals Gradient biomaterials and their influences on cell migration

2012 ◽  
Vol 2 (3) ◽  
pp. 337-355 ◽  
Author(s):  
Jindan Wu ◽  
Zhengwei Mao ◽  
Huaping Tan ◽  
Lulu Han ◽  
Tanchen Ren ◽  
...  
Keyword(s):  
Cell Migration ◽  
Regenerative Medicine ◽  
Tissue Regeneration ◽  
Cancer Metastasis ◽  
Healing Process ◽  
Immune Surveillance ◽  
The Body ◽  
Wound Healing Process ◽  
Driving Mechanism

Cell migration participates in a variety of physiological and pathological processes such as embryonic development, cancer metastasis, blood vessel formation and remoulding, tissue regeneration, immune surveillance and inflammation. The cells specifically migrate to destiny sites induced by the gradually varying concentration (gradient) of soluble signal factors and the ligands bound with the extracellular matrix in the body during a wound healing process. Therefore, regulation of the cell migration behaviours is of paramount importance in regenerative medicine. One important way is to create a microenvironment that mimics the in vivo cellular and tissue complexity by incorporating physical, chemical and biological signal gradients into engineered biomaterials. In this review, the gradients existing in vivo and their influences on cell migration are briefly described. Recent developments in the fabrication of gradient biomaterials for controlling cellular behaviours, especially the cell migration, are summarized, highlighting the importance of the intrinsic driving mechanism for tissue regeneration and the design principle of complicated and advanced tissue regenerative materials. The potential uses of the gradient biomaterials in regenerative medicine are introduced. The current and future trends in gradient biomaterials and programmed cell migration in terms of the long-term goals of tissue regeneration are prospected.

scholarly journals Maxillofacial-Derived Mesenchymal Stem Cells: Characteristics and Progress in Tissue Regeneration

2021 ◽  
Vol 2021 ◽  
pp. 1-22
Author(s):  
Xin Yan ◽  
Fei Yan ◽  
Hanan Abdulfattah Gamal Mohammed ◽  
Ousheng Liu
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Tissue Regeneration ◽  
Clinical Use ◽  
Regeneration Medicine ◽  
New Findings ◽  
Proliferation And Differentiation ◽  
The Common

Maxillofacial-derived mesenchymal stem cells (MFSCs) are a particular collective type of mesenchymal stem cells (MSCs) that originate from the hard and soft tissue of the maxillofacial region. Recently, many types of MFSCs have been isolated and characterized. MFSCs have the common characteristics of being extremely accessible and amazingly multipotent and thus have become a promising stem cell resource in tissue regeneration. However, different MFSCs can give rise to different cell lineages, have different advantages in clinical use, and regulate the immune and inflammation microenvironment through paracrine mechanisms in different ways. Hence, in this review, we will concentrate on the updated new findings of all types of MFSCs in tissue regeneration and also introduce the recently discovered types of MFSCs. Important issues about proliferation and differentiation in vitro and in vivo, up-to-date clinical application, and paracrine effect of MFSCs in tissue regeneration will also be discussed. Our review may provide a better guide for the clinical use of MFSCs and further direction of research in MFSC regeneration medicine.

Decellularized bone extracellular matrix in skeletal tissue engineering

2020 ◽  
Vol 48 (3) ◽  
pp. 755-764
Author(s):  
Benjamin B. Rothrauff ◽  
Rocky S. Tuan
Keyword(s):  
Tissue Engineering ◽  
Bone Regeneration ◽  
Tissue Regeneration ◽  
Animal Studies ◽  
Tumor Resection ◽  
Regenerative Capacity ◽  
Skeletal Tissue ◽  
Large Bone

Bone possesses an intrinsic regenerative capacity, which can be compromised by aging, disease, trauma, and iatrogenesis (e.g. tumor resection, pharmacological). At present, autografts and allografts are the principal biological treatments available to replace large bone segments, but both entail several limitations that reduce wider use and consistent success. The use of decellularized extracellular matrices (ECM), often derived from xenogeneic sources, has been shown to favorably influence the immune response to injury and promote site-appropriate tissue regeneration. Decellularized bone ECM (dbECM), utilized in several forms — whole organ, particles, hydrogels — has shown promise in both in vitro and in vivo animal studies to promote osteogenic differentiation of stem/progenitor cells and enhance bone regeneration. However, dbECM has yet to be investigated in clinical studies, which are needed to determine the relative efficacy of this emerging biomaterial as compared with established treatments. This mini-review highlights the recent exploration of dbECM as a biomaterial for skeletal tissue engineering and considers modifications on its future use to more consistently promote bone regeneration.

The Role of Polyphenols in the Modulation of Plasma Non-Enzymatic Antioxidant Capacity (NEAC)

2012 ◽  
Vol 82 (3) ◽  
pp. 228-232 ◽  
Author(s):  
Mauro Serafini ◽  
Giuseppa Morabito
Keyword(s):  
Antioxidant Capacity ◽  
Dietary Intervention ◽  
Ex Vivo ◽  
The Body ◽  
Dietary Polyphenols ◽  
Enzymatic Antioxidant ◽  
Endogenous Antioxidant

Dietary polyphenols have been shown to scavenge free radicals, modulating cellular redox transcription factors in different in vitro and ex vivo models. Dietary intervention studies have shown that consumption of plant foods modulates plasma Non-Enzymatic Antioxidant Capacity (NEAC), a biomarker of the endogenous antioxidant network, in human subjects. However, the identification of the molecules responsible for this effect are yet to be obtained and evidences of an antioxidant in vivo action of polyphenols are conflicting. There is a clear discrepancy between polyphenols (PP) concentration in body fluids and the extent of increase of plasma NEAC. The low degree of absorption and the extensive metabolism of PP within the body have raised questions about their contribution to the endogenous antioxidant network. This work will discuss the role of polyphenols from galenic preparation, food extracts, and selected dietary sources as modulators of plasma NEAC in humans.

Scintigraphic Detection of Experimental Myocardial Infarction with 99mTc-2,3-Dimercaptosuccinic Acid

1984 ◽  
Vol 23 (06) ◽  
pp. 317-319
Author(s):  
J. Novák ◽  
Y. Mazurová ◽  
J. Kubíček ◽  
J. Yižd’a ◽  
P. Kafka ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Coronary Artery ◽  
Intravenous Administration ◽  
Experimental Myocardial Infarction ◽  
Myocardial Infarctions ◽  
Clinical Use ◽  
Scintigraphic Imaging ◽  
Tissue Samples ◽  
Scintigraphic Finding

SummaryAcute myocardial infarctions were produced by ligature of the left frontal descending coronary artery in 9 dogs. The possibility of scintigraphic imaging with 99mTc-DMSA 4 hrs after intravenous administration was studied. The infarctions were 4, 24 and 48 hrs old. The in vivo scan was positive in only one dog with a 4-hr old infarction. The in vivo scans were confirmed by the analysis of the radioactivity in tissue samples. The accumulation of the radiopharmaceutical increased slightly in 48-hr old lesions; however, this increase was not sufficient for a positive scintigraphic finding. Thus, we do not recommend 99mTc-DMSA for clinical use in acute lesions.

Vorklinische Untersuchung zur Organverteilung und Strahlenbelastung von Radiojod-Jodlisurid

1991 ◽  
Vol 30 (04) ◽  
pp. 137-140
Author(s):  
H. Flade ◽  
B. Johannsen ◽  
V. Pink ◽  
U. Herold ◽  
R. Harhammer ◽  
...  
Keyword(s):  
Radiation Dose ◽  
The Body ◽  
Organ Distribution ◽  
Clinical Use ◽  
Isolated Organs

The distribution in rats of 125l-iodolisuride was studied. Three rats each were sacrificed at fixed intervals between 5 min and 24 h p. i., and the radioactivity was measured in isolated organs and parts of the body. The organ distribution and biexponential blood disappearance were similar to values for unlabeled lisuride. The radiation dose was estimated for man assuming a 123l label. The resulting doses were comparable to those from other radiopharmaceuticals in clinical use.

A Comparison of the in Vitro and in Vivo Thrombogenic Activity of Factor IX Concentrates Using Stasis (Wessler) and Non-Stasis Rabbit Models

1980 ◽  
Vol 44 (02) ◽  
pp. 081-086 ◽  
Author(s):  
C V Prowse ◽  
A E Williams
Keyword(s):  
Platelet Rich Plasma ◽  
Thrombus Formation ◽  
Factor Ix ◽  
Coagulation System ◽  
In Vitro Tests ◽  
Clinical Use ◽  
Low Activity

SummaryThe thrombogenic effects of selected factor IX concentrates were evaluated in two rabbit models; the Wessler stasis model and a novel non-stasis model. Concentrates active in either the NAPTT or TGt50 in vitro tests of potential thrombogenicity, or both, caused thrombus formation in the Wessler technique and activation of the coagulation system in the non-stasis model. A concentrate with low activity in both in vitro tests did not have thrombogenic effects in vivo, at the chosen dose. Results in the non-stasis model suggested that the thrombogenic effects of factor IX concentrates may occur by at least two mechanisms. A concentrate prepared from platelet-rich plasma and a pyrogenic concentrate were also tested and found to have no thrombogenic effect in vivo.These studies justify the use of the NAPTT and TGt50 in vitro tests for the screening of factor IX concentrates prior to clinical use.

Uptake, Internalization and Degradation of the Novel Plasminogen Activator Reteplase (BM 06.022) in the Rat

1995 ◽  
Vol 74 (06) ◽  
pp. 1501-1510 ◽  
Author(s):  
J Kuiper ◽  
H van de Bilt ◽  
U Martin ◽  
Th J C van Berkel
Keyword(s):  
Plasminogen Activator ◽  
Liver Cells ◽  
The Novel ◽  
Uptake Mechanism ◽  
Liver Uptake ◽  
Lysosomal Compartment ◽  
Β Phase ◽  
Α Phase ◽  
Parenchymal Liver

SummaryThe catabolism of the novel plasminogen activator reteplase (BM 06.022) was described. For this purpose BM 06.022 was radiolabelled with l25I or with the accumulating label l25I-tyramine cellobiose (l25I-TC).BM 06.022 was injected at a pharmacological dose of 380 μg/kg b.w. and it was cleared from the plasma in a biphasic manner with a half-life of about 1 min in the α-phase and t1/2of 20-28 min in the β-phase. 28% and 72% of the injected dose was cleared in the α-phase and β-phase, respectively. Initially liver, kidneys, skin, bones, lungs, spleen, and muscles contributed mainly to the plasma clearance. Only liver and the kidneys, however, were responsible for the uptake and subsequent degradation of BM 06.022 and contributed for 75% to the catabolism of BM 06.022. BM 06.022 was degraded in the lysosomal compartment of both organs. Parenchymal liver cells were responsible for 70% of the liver uptake of BM 06.022. BM 06.022 associated rapidly to isolated rat parenchymal liver cells and was subsequently degraded in the lysosomal compartment of these cells. BM 06.022 bound with low-affinity to the parenchymal liver cells (550 nM) and the binding of BM 06.022 could be displaced by t-PA (IC50 5.6 nM), indicating that the low-density lipoprotein receptor-related protein (LRP) could be involved in the binding of BM 06.022. GST-RAP, which is an inhibitor of LRP, could in vivo significantly inhibit the uptake of BM 06.022 in the liver.It is concluded that BM 06.022 is metabolized primarily in the liver and the kidneys. These organs take up and degrade BM 06.022 in the lysosomes. The uptake mechanism of BM 06.022 in the kidneys is unknown, while LRP is responsible for a low-affinity binding and uptake of BM 06.022 in parenchymal liver cells.

Toxicity of Heparinoids, with Special Reference to the Precipitation of Fibrinogen

1964 ◽  
Vol 12 (01) ◽  
pp. 232-261 ◽  
Author(s):  
S Sasaki ◽  
T Takemoto ◽  
S Oka
Keyword(s):  
Molecular Weight ◽  
Dextran Sulfate ◽  
Anticoagulant Activity ◽  
Molecular Structures ◽  
Severe Reaction ◽  
Clinical Use ◽  
Molecular Weights ◽  
Close Relationship

SummaryTo demonstrate whether the intravascular precipitation of fibrinogen is responsible for the toxicity of heparinoid, the relation between the toxicity of heparinoid in vivo and the precipitation of fibrinogen in vitro was investigated, using dextran sulfate of various molecular weights and various heparinoids.1. There are close relationships between the molecular weight of dextran sulfate, its toxicity, and the quantity of fibrinogen precipitated.2. The close relationship between the toxicity and the precipitation of fibrinogen found for dextran sulfate holds good for other heparinoids regardless of their molecular structures.3. Histological findings suggest strongly that the pathological changes produced with dextran sulfate are caused primarily by the intravascular precipitates with occlusion of the capillaries.From these facts, it is concluded that the precipitates of fibrinogen with heparinoid may be the cause or at least the major cause of the toxicity of heparinoid.4. The most suitable molecular weight of dextran sulfate for clinical use was found to be 5,300 ~ 6,700, from the maximum value of the product (LD50 · Anticoagulant activity). This product (LD50 · Anticoagulant activity) can be employed generally to assess the comparative merits of various heparinoids.5. Clinical use of the dextran sulfate prepared on this basis gave satisfactory results. No severe reaction was observed. However, two delayed reactions, alopecia and thrombocytopenia, were observed. These two reactions seem to come from the cause other than intravascular precipitation.

Inhibition of Fibrinolysis and Fibrinogenolysis in Man: Comparison of ε-Aminocaproic Acid and Kallikrein Inhibitor

1963 ◽  
Vol 10 (01) ◽  
pp. 106-119 ◽  
Author(s):  
E Beck ◽  
R Schmutzler ◽  
F Duckert ◽  
Keyword(s):  
Aminocaproic Acid ◽  
Side Reactions ◽  
In Vitro Tests ◽  
Factor V ◽  
Clinical Use ◽  
Strong Inhibitor ◽  
Kallikrein Inhibitor ◽  
Therapeutic Possibilities

SummaryInhibitor of kallikrein and trypsin (KI) extracted from bovine parotis was compared with ε-aminocaproic acid (EACA): both substances inhibit fibrinolysis induced with streptokinase. EACA is a strong inhibitor of fibrinolysis in concentrations higher than 0, 1 mg per ml plasma. The same amount and higher concentrations are not able to inhibit completely the proteolytic-side reactions of fibrinolysis (fibrinogenolysis, diminution of factor V, rise of fibrin-polymerization-inhibitors). KI inhibits well proteolysis of plasma components in concentrations higher than 2,5 units per ml plasma. Much higher amounts of KI are needed to inhibit fibrinolysis as demonstrated by our in vivo and in vitro tests.Combination of the two substances for clinical use is suggested. Therapeutic possibilities are discussed.

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