scholarly journals Adipose-Derived Stem Cells in Tissue Regeneration: A Review

2013 ◽  
Vol 2013 ◽  
pp. 1-35 ◽  
Author(s):  
Patricia Zuk

In 2001, researchers at the University of California, Los Angeles, described the isolation of a new population of adult stem cells from liposuctioned adipose tissue. These stem cells, now known as adipose-derived stem cells or ADSCs, have gone on to become one of the most popular adult stem cells populations in the fields of stem cell research and regenerative medicine. As of today, thousands of research and clinical articles have been published using ASCs, describing their possible pluripotency in vitro, their uses in regenerative animal models, and their application to the clinic. This paper outlines the progress made in the ASC field since their initial description in 2001, describing their mesodermal, ectodermal, and endodermal potentials both in vitro and in vivo, their use in mediating inflammation and vascularization during tissue regeneration, and their potential for reprogramming into induced pluripotent cells.

2014 ◽  
Vol 26 (1) ◽  
pp. 209
Author(s):  
Y. Zhang ◽  
C. Wei ◽  
P.-F. Zhang ◽  
X. Li ◽  
Y.-S. Li ◽  
...  

Somatic cells could be directly reprogrammed into stem state by ectopic expression of transcription factors, which share similar features of embryonic stem cells (ESC). Induced pluripotent stem cells (iPSC) possess promising application in producing genetically modified animals, whereas the generation of porcine offspring from iPSC is still difficult and controversial, and new materials are needed. In this study, we report the generation of iPSC from porcine adipose-derived stem cells (pADSC) using drug-inducible expression of defined human factors (Oct4, Sox2, Klf4, and c-Myc) and ‘2i’ plus leukemia inhibitory factor (LIF) culture system. pADSC were isolated from subcutaneous adipose tissue of a 28-day-old Danish Landrace, and subsequently characterised by high proliferation rate at low passages, long period passaging without significant replication senescence, mesenchymal stem cell-specific surface markers expression, including CD29 (0.995 ± 0.0577), CD44 (0.999 ± 0.0333), and CD90 (0.994 ± 0.0333), together with successful adipogenic and osteogenic differentiation ability in vitro. The reprogramming of iPSC from pADSC was evidently more efficient than the process from adult fibroblasts (P < 0.01), both of which were carried out under feeder-independent and serum-free conditions, and this may be due to the higher demethylation level of genomic DNA in pADSC. Two lines of porcine iPSC with naïve-like state were finally obtained through feeder-independent and serum-free conditions. The successful reprogramming of iPSC was demonstrated by short cell cycle interval, alkaline phosphatase (AP) staining positive, expression of stemness-related proteins including OCT-4, SOX2, NANOG, SSEA3, and SSEA4. Full reprogramming of iPSC was evaluated by the significant up-regulation of LIN28, ESRRB, UTF1, and DPPA5. Naïve-like state of porcine iPSC was further confirmed by the striking resemblance to naïve mESC, single-cell dissociation, LIF-dependency, up-regulation of STELLA and ERAS, and little translation of TRA-1-60 and TRA-1-81. In addition, porcine naïve-like iPSC possessed normal karyotypes, and could differentiate into cell types of all three germ layers in vitro and in vivo. Furthermore, in vivo studies to determine the capacity of these cells to integrate into the inner cell mass of blastocysts are still being undertaken for validation. Together, our study provided an efficient method to derive porcine naïve-like iPSC from pADSC, which may be useful for the production of living offspring. Y. Zhang and C. Wei contributed equally to this work. Y.-H. Zhang is the corresponding author. This work was supported by the National Natural Science Foundation Program 31272442.


2022 ◽  
Vol 119 (2) ◽  
pp. e2116865118
Author(s):  
Shiv Shah ◽  
Caldon Jayson Esdaille ◽  
Maumita Bhattacharjee ◽  
Ho-Man Kan ◽  
Cato T. Laurencin

Stem cells are of great interest in tissue regeneration due to their ability to modulate the local microenvironment by secreting bioactive factors (collectively, secretome). However, secretome delivery through conditioned media still requires time-consuming cell isolation and maintenance and also may contain factors antagonistic to targeted tissue regeneration. We have therefore engineered a synthetic artificial stem cell (SASC) system which mimics the paracrine effect of the stem cell secretome and provides tailorability of the composition for targeted tissue regeneration. We report the first of many applications of the SASC system we have formulated to treat osteoarthritis (OA). Choosing growth factors important to chondrogenesis and encapsulating respective recombinant proteins in poly (lactic-coglycolic acid) 85:15 (PLGA) we fabricated the SASC system. We compared the antiinflammatory and chondroprotective effects of SASC to that of adipose-derived stem cells (ADSCs) using in vitro interleukin 1B-induced and in vivo collagenase-induced osteoarthritis rodent models. We have designed SASC as an injectable therapy with controlled release of the formulated secretome. In vitro, SASC showed significant antiinflammatory and chondroprotective effects as seen by the up-regulation of SOX9 and reduction of nitric oxide, ADAMTS5, and PRG4 genes compared to ADSCs. In vivo, treatment with SASC and ADSCs significantly attenuated cartilage degeneration and improved the biomechanical properties of the articular cartilage in comparison to OA control. This SASC system demonstrates the feasibility of developing a completely synthetic, tailorable stem cell secretome which reinforces the possibility of developing a new therapeutic strategy that provides better control over targeted tissue engineering applications.


2010 ◽  
Vol 22 (1) ◽  
pp. 357 ◽  
Author(s):  
S. M. Wilson ◽  
E. Monaco ◽  
M. S. Goldwasser ◽  
S. G. Clark ◽  
W. L. Hurley ◽  
...  

Bone marrow is one current source of adult stem cells for therapeutic purposes; however, the magnitude and accessibility of subcutaneous adipose tissue in humans make it an attractive alternative. Numerous in vitro studies have been conducted to determine how these cells act in vitro, but it is imperative to determine the vast abilities of these cells in vivo. The objective of this study was to evaluate in vivo migration and bone healing ability after transplanting adipose-derived stem cells (ADSC) in a swine model. Adipose-derived stem cells were isolated from subcutaneous adipose tissue of adult Yorkshire pigs and cultured in vitro. At 80 to 90% confluence/passage 3, the cells were trypsinized and labeled in suspension with carboxyfluorescein succinimidyl ester (CFDA-SE). This project included 20 pigs weighing between 63.5 and 81.7 kg. Bilateral mandibular osteoectomies with 10-mm defects were performed on each pig. Of the 20 pigs, half received a treatment of 2.5 million CFDA-SE labeled stem cells administered directly into each defect (DI), and the remaining half received a treatment of approximately 5 million CFDA-SE labeled stem cells through an ear vein injection via catheter (EVI). The time points were 1 h and 2 and 4 wk, with 2 pigs per time with the DI and EVI treatments. Pigs were slaughtered at each time, and spleen, liver, lung, kidney, ear vein, blood, and mandible tissues were collected. Blood samples were collected from the jugular vein with EDTA and processed via flow cytometry after collection. Tissues were fixed in 10% buffered formalin for histology. Fluorescent microscopy (CFDA-SE excitation/emission is 492/517 nm) has confirmed that transplanted ADSC do indeed migrate to a site of injury or trauma. Labeled cells were also present in blood collected from the 1-h time point group. Currently, we have not seen the presence of labeled ADSC in the other tissues (spleen, liver, lung, and kidney) after the 1-h time point. We did observe that ADSC administered by DI and EVI were able to significantly heal and regenerate bone defects within 4 wk post-surgery (P < 0.05, ANOVA with F-test), in contrast to bone defects in pigs that did not receive cell injections (control). Evidence of ADSC-related healing and bone regeneration was evident by gross visualization, dual-energy x-ray absorptiometry (DXA) and micro computer tomography (microCT) analysis. The clinical implications of these results are significant for treating many diseases in which inflammation or defects exist, such as cardiac disease, neurological disease, or traumatic injuries to both soft and hard tissue. If the adult stem cells can be harvested from fat, encouraged to produce bone or cartilage, and then reinserted into defects, treatment protocols for trauma victims could be developed that would reduce the need for alternate harvesting techniques for bone. This work was support by a grant from the Illinois Regenerative Medicine Institute (IDPH # 63080017).


2010 ◽  
Vol 22 (1) ◽  
pp. 347
Author(s):  
N. Cieslak ◽  
A. Massie ◽  
S. M. Wilson ◽  
E. Monaco ◽  
M. B. Wheeler

The quantity, accessibility, and abundance of subcutaneous adipose tissue in humans make it an attractive alternative to bone marrow as a source of adult stem cells for therapeutic purposes. Adult adipose-derived mesenchymal stem cells can differentiate into a variety of lineages including adipose, bone, cartilage, and muscle. In addition, the use of adult stem cells for regenerative medicine rather than those from embryos avoids concerns with ethics, safety, and immunology. One important issue is the ability to track the transplanted stem cells during the regeneration process to evaluate the stem cell-mediated healing. The objective of this study was to compare the efficiency, longevity, and intensity of carboxyfluorescein diacetate, succinimidyl ester (CFDA SE) and quantum dot nanocrystal (Qtracker™, Invitrogen, Carlsbad, CA, USA) labeled adipose-derived stem cells (ADSC) over an in vitro culture period of 4 weeks. Adipose-derived stem cells (6 x 106) previously isolated and frozen at -196°C were thawed and cultured in 75-cm3 flasks with 14 mL of DMEM. Cells were grown to 80% confluence and trypsinized. After trypsinization, the cells were divided into 4 treatments (3 x 106 cells per treatment). The treatments were (1) unlabeled control, (2) labeled with 30 μM CFDA SE, (3) labeled with 15 nM Qtracker™, and (4) labeled with 15 nM Qtracker™, following the Invitrogen Qtracker™ protocol. Cells (1 x 106) were removed from each treatment every week for 4 weeks and fixed in formalin for later analysis. When all the samples were collected, they were analyzed using flow cytometry. Data were analyzed via chi-square test. The percentage of cells labeled with CFDA SE and Qtracker™ was 99.35 and 98.46%, respectively, immediately after labeling. By 1 wk, the percentage of cells labeled with CFDA SE and Qtracker™ had deceased (P < 0.01) to 0.11 and 1.48%, respectively. The CFDA SE-labeled cell percentages had decreased (P < 0.01) to 0% at 2, 3, and 4 wk, respectively. The Qtracker™-labeled cells also decreased (P < 0.01) to 0.745, 1.69 and 0.45% at 2, 3, and 4 wk, respectively. The high rate of cell division of these cells in vitro might be responsible for the rapid loss of both labels during the first week of culture. Previous results from our lab have shown that the CFDA SE is retained in the cells for up to 6 wk in vivo (Lima AS et al. 2006 Reprod. Fertil. Dev. 18, 208). Similar studies need to be done with the quantum dot-labeled cells to determine the Qtracker™ label’s longevity in vivo. In conclusion, quantum dots can be used to label ADSC, in vitro, for at least 4 wk, albeit at much lower levels than those observed during the week following labeling. Determination of a suitable label for high-percentage porcine ADSC labeling during long-term in vitro culture remains to be completed. This research was supported by the Intel Scholar’s Program and the Illinois Regenerative Medicine Institute.


2016 ◽  
Vol 12 ◽  
pp. 38-47 ◽  
Author(s):  
Aleksandra Skubis ◽  
Bartosz Sikora ◽  
Nikola Zmarzły ◽  
Emilia Wojdas ◽  
Urszula Mazurek

This review article provides an overview on adipose-derived stem cells (ADSCs) for implications in bone tissue regeneration. Firstly this article focuses on mesenchymal stem cells (MSCs) which are object of interest in regenerative medicine. Stem cells have unlimited potential for self-renewal and develop into various cell types. They are used for many therapies such as bone tissue regeneration. Adipose tissue is one of the main sources of mesenchymal stem cells (MSCs). Regenerative medicine intends to differentiate ADSC along specific lineage pathways to effect repair of damaged or failing organs. For further clinical applications it is necessary to understand mechanisms involved in ADSCs proliferation and differentiation. Second part of manuscript based on osteogenesis differentiation of stem cells. Bones are highly regenerative organs but there are still many problems with therapy of large bone defects. Sometimes there is necessary to make a replacement or expansion new bone tissue. Stem cells might be a good solution for this especially ADSCs which manage differentiate into osteoblast in in vitro and in vivo conditions.


2020 ◽  
Vol 2020 ◽  
pp. 1-24 ◽  
Author(s):  
Israa Ahmed Radwan ◽  
Dina Rady ◽  
Marwa M. S. Abbass ◽  
Sara El Moshy ◽  
Nermeen AbuBakr ◽  
...  

Cell-based therapies currently represent the state of art for tissue regenerative treatment approaches for various diseases and disorders. Induced pluripotent stem cells (iPSCs), reprogrammed from adult somatic cells, using vectors carrying definite transcription factors, have manifested a breakthrough in regenerative medicine, relying on their pluripotent nature and ease of generation in large amounts from various dental and nondental tissues. In addition to their potential applications in regenerative medicine and dentistry, iPSCs can also be used in disease modeling and drug testing for personalized medicine. The current review discusses various techniques for the production of iPSC-derived osteogenic and odontogenic progenitors, the therapeutic applications of iPSCs, and their regenerative potential in vivo and in vitro. Through the present review, we aim to explore the potential applications of iPSCs in dental and nondental tissue regeneration and to highlight different protocols used for the generation of different tissues and cell lines from iPSCs.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Lei Wang ◽  
Shaojie Shi ◽  
Ruiping Bai ◽  
Yue Wang ◽  
Zhao Guo ◽  
...  

Abstract Background Patients with type 2 diabetes mellitus (T2DM), especially those with poor glycemic control, are characterized by low bone mass and destruction of bone microstructure. Nowadays, autologous mesenchymal stem cells (auto-MSCs) have been used to repair defects and promote tissue regeneration due to handy source, low immunogenicity and self-renewing and multi-differentiating potential. However, T2DM changed the biological properties of auto-MSCs, and investigating the most suitable auto-MSCs for T2DM patients becomes a focus in tissue engineering. Results In this research, we compared the biological characteristics of adipose-derived stem cells (ASCs) and bone marrow stem cells (BMSCs) derived from T2DM rats. These results demonstrated that ASCs had a higher proliferation rate, colony-formation and cell-sheet forming ability, while BMSCs got better osteogenesis-related staining, expression of osteogenesis-related genes and proteins, and osteogenic capacity in vitro. Conclusions As it turned out, ASCs from T2DM had a higher proliferation, while BMSCs had significantly higher osteogenetic ability no matter in vitro and in vivo. Therefore, we should take into account the specific and dominated properties of MSC according to different needs to optimize the protocols and improve clinical outcomes for tissue regeneration of T2DM patients.


Reproduction ◽  
2015 ◽  
Vol 149 (5) ◽  
pp. 485-496 ◽  
Author(s):  
Chao Wei ◽  
Xia Li ◽  
Pengfei Zhang ◽  
Yu Zhang ◽  
Tong Liu ◽  
...  

Partially reprogrammed induced pluripotent stem cells (PiPSCs) have great potential for investigating reprogramming mechanisms and represent an alternative potential material for making genetically modified animals and regenerative medicine. To date, PiPSCs have scarcely been reported in detail when compared with mice and humans. In this study, we obtained PiPSCs from porcine adipose-derived stem cells (pADSCs) by ectopic expression of human transcription factors (OCT4, SOX2, c-MYC, and KLF4) in feeder-free condition. The morphology and proliferation activity of porcine PiPSCs (pPiPSCs) were similar to those of porcine fully reprogrammed iPSCs (pFiPSCs); furthermore, pPiPSCs expressed higher levels of the typical surface molecules (CD29) found in pADSCs. However, pPiPSCs were negative for key proteins (NANOG) connected with stemness and possessed lower differentiation ability in vivo and in vitro. When differentiation-inhibiting factors were withdrawn, pPiPSCs-derived cells (pPiPSC-DCs) showed similar features to pADSCs in many aspects, including proliferation, differentiation, and immunosuppression. When both types of cells were used to produce cloned embryos, we found that the blastocyst formation rate of 19DC (one of the pPiPSC-DC cell lines)-derived cloned embryos was obviously higher than that of others. The total cell number of 19DC-derived blastocysts was significantly higher than the 30DC (one pFiPSC-DC cell line)-derived blastocysts. In all, through limited differentiation ability, the proliferation activity of pPiPSCs is similar to that of pFiPSCs, and pPiPSCs can retain several of the features of pADSCs, which are beneficial to cell therapy. Furthermore, the differentiation of pPiPSCs is more favorable for producing high-quality reconstructed embryos.Free Chinese abstract: A Chinese translation of this abstract is freely available at http://www.reproduction-online.org/content/149/5/485/suppl/DC2.


2021 ◽  
Vol 30 ◽  
pp. 096368972110354
Author(s):  
Eun-Jung Yoon ◽  
Hye Rim Seong ◽  
Jangbeen Kyung ◽  
Dajeong Kim ◽  
Sangryong Park ◽  
...  

Stamina-enhancing effects of human adipose derived stem cells (hADSCs) were investigated in young Sprague-Dawley rats. Ten-day-old male rats were transplanted intravenously (IV) or intracerebroventricularly (ICV) with hADSCs (1 × 106 cells/rat), and physical activity was measured by locomotor activity and rota-rod performance at post-natal day (PND) 14, 20, 30, and 40, as well as a forced swimming test at PND 41. hADSCs injection increased the moving time in locomotor activity, the latency in rota-rod performance, and the maximum swimming time. For the improvement of physical activity, ICV transplantation was superior to IV injection. In biochemical analyses, ICV transplantation of hADSCs markedly reduced serum creatine phosphokinase, lactate dehydrogenase, alanine transaminase, and muscular lipid peroxidation, the markers for muscular and hepatic injuries, despite the reduction in muscular glycogen and serum triglycerides as energy sources. Notably, hADSCs secreted brain-derived neurotrophic factor (BDNF) and nerve growth factor in vitro, and increased the level of BDNF in the brain and muscles in vivo. The results indicate that hADSCs enhance physical activity including stamina not only by attenuating tissue injury, but also by strengthening the muscles via production of BDNF.


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