scholarly journals ID: 1055 Adipose-derived stem cells and platelet rich plasma ameliorate liver cirrhotic circumstance in CCl4-induced mice: a new approach for liver cirrhosis treatment

2017 ◽  
Vol 4 (S) ◽  
pp. 136
Author(s):  
Nhung Hai Truong ◽  
Nam Hai Nguyen ◽  
Trinh Van Le ◽  
Nghia Huynh ◽  
Dat Quoc Ngo ◽  
...  

Background: Stem cell therapy in liver cirrhosis treatment is attracting the attention of the scientific community. Adipose tissue-derived mesenchymal stem cells are a potential source of cells because they have self-renewal, high proliferation, and differentiation into a variety of cell types, including hepatocytes as potential cell sources for cirrhosis treatment. Platelet-rich plasma (PRP) growth factors contribute to regeneration and wound healing. We test the hypothesis that PRP co-administration enhances MSC treatment for mouse cirrhosis. Method: Male Swiss mice were treated orally with olive oil or CCl4 for 11 weeks. PRP was obtained from healthy mice. Mouse adipose-derived stem cells (mADSCs) from adipose tissue of 3 weeks CCl4 mice were cultured for three passages (P3-mADSCs) before the transfer by tail vein injection with or without PRP into 11 weeks CCl4 mice. Mice were divided into six groups (n=10 each group). 1) normal, 2) cirrhotic, 3) cirrhotic /PBS; 4) cirrhotic/PRP (0.2 ml/mice with PRP from healthy mice), 5) cirrhotic/mADSCs (5 x 105 cells/mice), and 6) cirrhotic/mADSC-PRP.   Result: mADSCs were highly positive for CD44, CD90, and CD105. Relative to liver cells, P3-mADSCs highly expressed Alb, Ck18, Ck19, Tnf, c-met, Cyp1a1, Afp, Muc1, Ldl receptor. mADSCs were strongly positive for Cyp1a1 (98.21±1.57%) and Hgf (95.55±3.11%); moderately positive for alfa-fetoprotein (45.99±2.08%), Aat (44.43±7.79%), Alb (57.81±8.49%) and differentiated into hepatocyte-like cells under induction medium. After transplantation, CFDA-transplanted cells into CCl4-treated mice were found in the liver at day 21 st. Compared to mADSCs, mADSCs and PRP co-treatment most effectively improved serum AST/ALT/bilirubin and albumin levels in day seven cirrhotic mice (p<0.05); and significantly down-regulated procollagen (104-fold less) and TGF-beta 1 (10-fold less) in day 21 cirrhotic liver. Histology index and collagen deposition were improved in 100% of mADSC/PRP- and mADSCs- cirrhotic mice compared to 33.3% of PBS- or PRP- cirrhotic liver (p<0.05). Conclusion: Cultured mADSCs express hepatocyte enriched markers. PRP coadministration enhances mADSC effects to improve liver function further, and further reduce fibrosis.

Cartilage regenerative medicine has been met with much interest due to their ability to inhibit disease progression of osteoarthritis (OA). The use of adipose-derived stem cells has been suggested as a reliable method for OA treatment because of their potential to differentiate into a variety of cell lines and their potent capability to self-renewal and repair. The aim of this study is to assess adipose-derived stem cells in combination with PRP ability in treating a patient with knee OA. A 53-year- old man with osteoarthritis was selected for this treatment. Human abdominal subcutaneous adipose sample was obtained from a patient with knee OA. Stem cells were obtained from adipose tissue of abdominal origin by digesting lipoaspirate tissue with collagenase. ADSCs cultured in DMEM medium supplemented with 10% FBS. Also, ADSCs expanded and characterized by flow cytometry. These stem cells, along with platelet-rich plasma and calcium chloride, were injected into the right knee. Pre-treatment and post-treatment MRI scans, physical therapy, and pain score data were then analyzed. The MRI data for the patient demonstrated significant positive changes. Probable cartilage regeneration was sensible in the patient. Along with MRI evidence, the measured physical therapy outcomes, subjective pain, and functional status all improved. Autologous adipose-derived stem cell injection, in conjunction with platelet-rich plasma is a promising minimally invasive therapy for osteoarthritis of human knees. The present clinical case report demonstrated that a combination of percutaneous injection of autologous ADSCs and PRPmay be able to regenerate cartilage in human knee OA.


2006 ◽  
Vol 18 (2) ◽  
pp. 171
Author(s):  
T. Davidson ◽  
S. Lane ◽  
C. Ferguson ◽  
M. Wheeler ◽  
W. Hurley

Porcine mammary tissue is a dynamic system that undergoes multiple cycles of growth, differentiation, and regression during the life cycle of a female; however, the mechanisms of mammary morphogenesis are not fully understood. The current hypothesis suggests that epithelial stem cells in the terminal end buds interact with surrounding epithelial and stromal cells during mammary tissue development and regeneration. Because the mammary gland of the virgin animal consists largely of a pad of adipose tissue, we propose that adipose-derived stem cells from the mammary fat pad (MFP) may also play a role in the regeneration process. Therefore, the objective of this experiment was to determine whether multilineage stem cells are present in the MFP of gilts. Adipose tissue from the MFP and back fat (BF) from the loin region were harvested from six nulliparous, cycling Yorkshire gilts, approximately 16 mo of age. Methods for isolation of adipose-derived stem cells were modified from those of Malusky and Wheeler (2004; International Society for Stem Cell Research, Proceedings 2nd Annual Meeting, abstr. 248:124). Presumptive stem cells isolated from each tissue type were maintained in vitro in DMEM supplemented with either 10% newborn calf serum (NCS; Rep 1 and 2) or 10% fetal calf serum (Rep 3). BF and MFP cell types formed colonies of fibroblast-like cells within 3 to 5 d. Growth characteristics are shown in Table 1. When the cells were 80% confluent, they were trypsinized and reseeded into 75-cm2 flasks. When cultured in the presence of NCS, both cell types had a progressive decrease in viability, and these cultures could not be maintained past Passage 4. Differentiation of both cell types (Passage 1) into adipogenic, myogenic, and osteogenic lineages are currently underway. Based on morphological evaluations, both cell types are able to differentiate into the aforementioned lineages; however, differentiation of MFP-derived cells occurred at a slower rate and was less pronounced than that of BF-derived cells. These preliminary findings suggest that the MFP likely contains a population of multipotent stem cells; however, at this time, it is not possible to make meaningful statistical comparisons. Further experiments are needed to fully characterize these cells and determine their role in mammary gland morphogenesis. Table 1. Growth of porcine adipose-derived stem cells obtained from the BF or from the MFP This study was partially supported by the Council for Food and Agricultural Research (C-FAR) Sentinel Program and USDA Multistate Project (W-1171).


2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Federica Rey ◽  
Elena Lesma ◽  
Daniela Massihnia ◽  
Emilio Ciusani ◽  
Sara Nava ◽  
...  

Mesenchymal stem cells (MSCs) are multipotent cells able to differentiate into multiple cell types, including adipocytes, osteoblasts, and chondrocytes. The role of adipose-derived stem cells (ADSCs) in cancers is significantly relevant. They seem to be involved in the promotion of tumour development and progression and relapse processes. For this reason, investigating the effects of breast cancer microenvironment on ADSCs is of high importance in order to understand the relationship between tumour cells and the surrounding stromal cells. With the current study, we aimed to investigate the specific characteristics of human ADSCs isolated from the adipose tissue of breast tumour patients. We compared ADSCs obtained from periumbilical fat (PF) of controls with ADSCs obtained from adipose tissue of breast cancer- (BC-) bearing patients. We analysed the surface antigens and the adipogenic differentiation ability of both ADSC populations. C/EBPδ expression was increased in PF and BC ADSCs induced to differentiate compared to the control while PPARγ and FABP4 expressions were enhanced only in PF ADSCs. Conversely, adiponectin expression was reduced in PF-differentiated ADSCs while it was slightly increased in differentiated BC ADSCs. By means of Oil Red O staining, we further observed an impaired differentiation capability of BC ADSCs. To investigate this aspect more in depth, we evaluated the effect of selective PPARγ activation and nutritional supplementation on the differentiation efficiency of BC ADSCs, noting that it was only with a strong differentiation stimuli that the process took place. Furthermore, we observed no response in BC ADSCs to the PPARγ inhibitor T0070907, showing an impaired activation of this receptor in adipose cells surrounding the breast cancer microenvironment. In conclusion, our study shows an impaired adipogenic differentiation capability in BC ADSCs. This suggests that the tumour microenvironment plays a key role in the modulation of the adipose microenvironment located in the surrounding tissue.


2020 ◽  
Vol 5 (4) ◽  
pp. 175
Author(s):  
Karina Karina ◽  
Imam Rosadi ◽  
Wismo Reja Subroto ◽  
Alfida Zakiyah ◽  
Irsyah Afini ◽  
...  

<p>Abstrak - <strong>Mesenchymal Stem Cells (MSCs) merupakan sel yang memiliki kemampuan memperbarui diri dan berdiferensiasi menjadi berbagai jenis sel. MSCs berperan penting dalam perbaikan dan regenerasi jaringan. Adipose-Derived Stem Cells (ADSCs) merupakan MSCs yang didapatkan dari jaringan lemak. ADSCs telah banyak digunakan dalam studi MSCs karena ketersediaan sumber sel yang banyak dalam jaringan tubuh dan proses isolasinya lebih mudah serta memiliki risiko yang lebih rendah. Pada studi ini, ADSCs digunakan untuk mengetahui kemampuan migrasi dalam medium yang mengandung fetal bovine serum 10% (FBS) dengan penambahan L-Ascorbic Acid (LAA) konsentrasi 0%, 1%, 3% dan 6%. Kuantifikasi kemampuan migrasi dilakukan dengan menggunakan teknik goresan luka. ADSCs yang dikulturkan menunjukkan morfologi seperti fibroblas. Luas penutupan luka menunjukkan hasil tertinggi dengan perbedaan yang tidak signifikan pada penambahan konsentrasi LAA 3% dan 6% dibandingkan penambahan LAA 0%, 1% dan kontrol. Hasil ini juga ditunjukkan pada pasase 7, 8, dan 9. ADSCs menunjukkan kemampuan migrasi yang optimal pada penambahan LAA 3% dan 6% dibandingkan medium dengan penambahan LAA 0%, 1% dan kontrol.</strong></p><p>Abstract - <strong>Mesenchymal stem cells (MSCs) are multilineage cells with the ability to self-renew and differentiate into a variety of cell types. MSCs play important role in tissue repair and regeneration. Adipose-Derived Stem Cells (ADSCs) are MSCs derived from fat tissue. ADSCs has been widely used in MSCs studies because it require more cell sources in body tissue and the process of isolation is easier and has lower risk. In this study, ADSCs were used to determine migration ability in a medium containing 10% bovine fetal serum (FBS) using 0%, 1%, 3% and 6% of L-Ascorbic Acid (LAA) concentrations. Quantification of migration ability was done by using scratch technique. ADSCs were cultured display fibroblasts-like morphology. The closure of wound area is highest with not significantly difference in LAA concentrations of 3% and 6% compared to LAA 0%, 1% and control. This results were also showed on 7, 8, and 9 cell passage. ADSCs showed optimal migration ability at LAA 3% and 6% compared to media with LAA 0%, 1% and control.</strong></p><p><strong>Keywords - <em>ADSCs, Cells Migration, LAA</em></strong><em>.</em></p>


2015 ◽  
Vol 21 (5-6) ◽  
pp. 895-905 ◽  
Author(s):  
Satoshi Tajima ◽  
Morikuni Tobita ◽  
Hakan Orbay ◽  
Hiko Hyakusoku ◽  
Hiroshi Mizuno

Biomaterials ◽  
2007 ◽  
Vol 28 (26) ◽  
pp. 3834-3842 ◽  
Author(s):  
Lauren Flynn ◽  
Glenn D. Prestwich ◽  
John L. Semple ◽  
Kimberly A. Woodhouse

2020 ◽  
Author(s):  
Yoshio Sakai ◽  
Shinya Fukunishi ◽  
Masayuki Takamura ◽  
Oto Inoue ◽  
Shinichiro Takashima ◽  
...  

BACKGROUND Liver cirrhosis results from chronic hepatitis, and is characterized by advanced fibrosis due to long-term hepatic inflammation. Cirrhosis ultimately leads to manifestations of jaundice, ascites, and encephalopathy, and increases the risk of hepatocellular carcinoma. Once cirrhosis is established, resulting in hepatic failure, no effective treatment is available. Therefore, novel therapies to inhibit disease progression of cirrhosis are needed. OBJECTIVE The objective of this investigator-initiated clinical trial is to assess the safety and efficacy of autologous adipose tissue-derived regenerative (stem) cell therapy delivered to the liver via the hepatic artery in patients with liver cirrhosis. METHODS Through consultation with the Japan Pharmaceuticals and Medical Devices Agency, we designed a clinical trial to assess a therapy for liver cirrhosis based on autologous adipose tissue-derived regenerative (stem) cells, which are extracted using an adipose tissue dissociation device. The primary endpoints of the trial are the serum albumin concentration, prothrombin activity, harmful events, and device malfunction. RESULTS Enrollment and registration were initiated in November 2017, and the follow-up period ended in November 2019. Data analysis and the clinical study report will be completed by the end of March 2020. CONCLUSIONS Completion of this clinical trial, including data analysis, will provide data on the safety and efficacy of this novel liver repair therapy based on autologous adipose tissue-derived regenerative (stem) cells using an adipose tissue dissociation device. CLINICALTRIAL UMIN Clinical Trials Registry UMIN000022601; https://tinyurl.com/w9uqw3q INTERNATIONAL REGISTERED REPORT DERR1-10.2196/17904


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