Fetal Stem Cell

Fetal stem cell therapy provides access to hematopoietic stem cell niches at an important time in evolution when stem cells are migrating to their destined tissues and offers the ability to treat a disease before nativity.

From: Perinatal Genetics , 2019

Stem Cell Research

Padma Nambisan , in An Introduction to Ethical, Safety and Intellectual Property Rights Problems in Biotechnology, 2017

3.2.iii Fetal Stalk Cells

Fetal stalk cells were first isolated and cultured by John Gearhart and his squad at the Johns Hopkins Academy School of Medicine in 1998 ( Shamblott et al., 1998). These cells known equally primordial germ cells are the precursors of eggs and sperms and were isolated from the gonadal ridges and mesenteries of 5–9-calendar week fetuses obtained past therapeutic abortion. Embryonic germ (EG) cells isolated from them are constitute to exist pluripotent. Issues associated with isolation of these stem cells are (1) they can be obtained only from 8- to 9-week-old fetuses and (2) EG cells take limited proliferation capacity.

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Fetal Tissues

Ryan P. Dorin , Chester J. Koh , in Principles of Regenerative Medicine (Second Edition), 2011

Stem Cells Derived from Fetal Tissues

Fetal stem cells are not a new concept and in fact they accept been in clinical utilize over the past 20 years, though not consistently in the field of tissue engineering. These cells display many properties that make them superior to adult cells for employ in regenerative medicine applications, including greater plasticity in differentiation potential, faster growth in culture, and increased survival at low oxygen tension. Fetal cells have also been observed to produce loftier levels of angiogenic and trophic factors, resulting in improved growth in vivo and facilitating regeneration of surrounding host tissues (Turner and Fauza, 2009).

The three virtually reliable sources to engagement of abundant fetal stalk cells are the placenta, amniotic fluid, and umbilical cord claret. These sources are also attractive in that their stem cells are obtained in a minimally invasive fashion from the fetus. Samples from amniotic fluid and the placenta are retrieved using the common prenatal diagnostic procedures of amniocentesis and chorionic villous sampling, whose fetal complexity rates are estimated at 0.5% (Evans and Wapner, 2005). Umbilical cord blood is easily obtained at the fourth dimension of birth and can be easily preserved in cord claret banks. Indeed, at that place are currently over 400,000 units of string blood banked worldwide (Kurtzberg, 2009). Other fetal progenitor cell sources that have been investigated include bone marrow (Michejda, 2004), neural tissue (Lindvall and Bjorklund, 2004), liver (Dabeva and Shafritz, 2003), kidney (Al-Awqati and Oliver, 2002; Rollini et al., 2004), and lung (in't Anker et al., 2003).

Amniotic fluid is unique among these sources in that it contains a wide array of cell types, owing to its constantly irresolute composition throughout gestation. Ship of fluid across fetal pare, respiratory secretions, fetal urination, and fetal swallowing and gastrointestinal (GI) excretions all contribute to the makeup of amniotic fluid. This results in the presence of fetal skin, respiratory, urinary tract, and GI tract cells in the aminotic fluid mileu, as well equally embryonic cells from all three germ layers – endoderm, mesoderm, and ectoderm. Other fetal cell types may likewise be present in certain pathologic states, such as nervus cells in the case of a fetus with a neural tube defect. The presence of pluripotent stem cells in amniotic fluid was suggested in a report by Sancho and colleagues in 1993, who demonstrated differentiation of aminotic fluid cells to myoblasts using viral transfection of a cistron regulating myogenesis (Sancho et al., 1993). The power of these cells, known equally mesenchymal stalk cells (MSCs), to differentiate into cells of all three germ cell layers has been demonstrated much more recently, making them well suited to tissue engineering applications (Tsai et al., 2006; de Coppi et al., 2007; Holden, 2007).

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Fetal Tissues

Seyung Chung , Chester J. Koh , in Principles of Regenerative Medicine, 2008

STEM CELLS DERIVED FROM FETAL TISSUES

Fetal stem cells are not a new concept and in fact they have been in clinical use over the past 10 to twenty years. For instance, umbilical string claret (UCB) stem cells are widely used in the treatment of hematological disorders ( Watt and Contreras, 2005), and fetal neural tissue has been associated with some clinical improvement in the handling of Parkinson's disease (Lindvall and Bjorklund, 2004). Several sources of stem cells derived from fetal tissues accept been investigated, and a select few are listed below.

For hematopoiesis, fetal bone marrow, every bit opposed to adult os marrow, cord claret, or peripheral blood, appears to be the ideal source of stem cells for engraftment and therapeutic reconstitution, as they take a very loftier proliferative capacity, low immunogenicity, and the highest number of archaic stalk/progenitor cells (Michejda, 2004).

Every bit transplanted mature hepatocytes accept enormous repopulating capacity nether weather condition of continuous liver injury, progenitor cells from fetal liver cells have been isolated and transplanted, where upwards to 10% of a normal liver can be repopulated (Dabeva and Shafritz, 2003; Rollini et al., 2004). Withal, further studies are necessary to make up one's mind the regenerative capabilities of these cells for both liver regeneration besides every bit for other mesenchymal tissues.

Mesenchymal stalk cells (MSCs) have been isolated from human being fetal blood, liver, and bone marrow, where they exhibited clonogenicity and were able to differentiate into the adipogenic, osteogenic, and chondrogenic lineages (Campagnoli et al., 2001). The fetal kidney may too be a potential source of MSCs, since the metanephric mesenchyme may correspond a pluripotent population with a predilection toward the epithelial and stromal cell lineages (Al-Awqati and Oliver, 2002). Second-trimester fetal lung was besides noted to be a source of MSCs, specially for the osteogenic and adipogenic lineages (in 't Anker et al., 2003).

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Regenerative Medicine of the Bladder

Yuanyuan Zhang , Anthony Atala , in Principles of Regenerative Medicine (Tertiary Edition), 2019

Prison cell Expansion

Fetal stem cells, such as amniotic fluid and primitive stem cells (such as placenta-derived stem cells), showed promise for hereafter clinical applications [47,48]. These cells can develop into cells from the endoderm, mesoderm, and ectoderm and can be maintained for over 250 population doubling (PD). Long telomeres are retained and a normal karyotype without tumorigenicity is observed in vivo [49]. Adult stem cells have been successfully isolated from various types of tissues. These cells usually reach a PD charge per unit of 20–xl in 10 passages [xix].

USCs can generate large numbers of cells in a single clone [twenty,39]. Around 100–140 USC clones can be formed from 24-h urine collection from one individual [l]. Up to 75% of these cells are highly proliferative owing to their relatively higher telomerase activity (USC-TA+) and longer telomeres compared with BMSCs [20]. USCs are reported to accept a PD rate of threescore–seventy for up to 20 passages, whereas other USCs without telomerase activity can exist maintained for 8–x passages with 34 population doublings. Based on this ratio of cells and urine volume, ii urine samples containing 20–thirty USC clones could potentially yield at least ane.5   ×   109 USCs at the terminate of passage 4 within iv–five   weeks [v,38].

Isolation of USCs is a separation- and digestion-gratis procedure. Urine samples are simply centrifuged and cells are seeded in mixed media equanimous of keratinocyte serum-free medium and embryonic fibroblast medium at a 1:i ratio [34]. Expanded USCs are a relatively homogeneous population and require only 2–five% serum to exist maintained in vitro; past contrast, nearly MSCs crave 10–20% serum [20]. When cells collected from voided urine are cultured in USC civilization media, only USCs tend to attach to the civilization container and continuously expand in civilization [9]. This quick, easy, and economical procedure for USC isolation may also facilitate their large-scale expansion for potential clinical trials.

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Bioartificial Liver

Southward.L. Nyberg , ... J.M. Glorioso , in Pathobiology of Homo Disease, 2014

Liver Stalk Cells

Liver-derived stem cells (fetal liver cells or adult liver stem cells) take been used to generate master hepatocytes. Fetal liver cells (hepatoblasts) are bipotent cells which tin differentiate into both hepatocytes and biliary cells. These cells have been demonstrated to engraft and differentiate into marine hepatocytes post-obit transplantation into immunodeficient mice. The adult liver is known for its regenerative potential. Fifty-fifty when hepatocytes are experimentally limited in their regenerative potential, the hepatic bipotent progenitor cells (oval cells) retain the ability to expand and differentiate resulting in liver regeneration. Unfortunately the cell mass of hepatoblasts is less than 0.ane% of fetal liver mass and oval cells contain 0.3–0.7% of adult liver mass, severely limiting the potential of these cells for large-scale hepatocyte production.

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Embryonic

Michele Boiani , Hans Schöler , in Handbook of Stem Cells, 2004

Nuclear Transfer from Fetal Stalk Cells

To date, overt fetal stalk cells take not been bachelor every bit nucleus donors for mouse cloning, and the effect of if, when, and how fetal stalk cells were used as nucleus donors is controversial. Neuronal stem cells may have been used for cloning serendipitously. Yamazaki and colleagues 34 tested neural cells dissected from different regions of the fetal brain (15.5–17.5 days postcoitus [dpc]). Clone pups were consistently derived from immature neural stages (V cortical zone; 5.8% of the reconstructed oocytes developed to term) merely not from postmitotic differentiated stages (P cortical zone; 0.five%). This suggested a large decline in the dominance of neurons to support normal development after their migration from V to P zone, which is completed subsequently birth and probably accounts for the initial 7 and confirmed 40 disability to successfully clone mice directly from brain cells. Interestingly, there were no significant differences in the rates of preimplantation evolution and development upwardly to mid–gestation-stage clones derived from fetal versus adult brain cells.

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In Utero Therapy for Congenital Disorders Using Amniotic Fluid Stem Cells

Sindhu Subramaniam , ... Anna L. David , in Perinatal Stem Cells, 2018

Reprogramming of Amniotic Fluid Stem Cells

AFSCs are highly proliferating fetal stalk cells with broad differentiation potential adjoining on pluripotency, which characteristically make them ideal for reprogramming. Upgrading to pluripotency confers unlimited proliferation and differentiation potential without inducing senescence. The C-kit+ AFSCs which comprise effectually i% of the multipotent cells in the AF share 82% transcriptome identity with human embryonic stem cells (hESCs) and express pluripotency markers such equally Oct4, Sox2, KLF4, SSEA-3, TRA 160, TRA 181 only do not form teratomas [49]. AFS mesenchymal cells which comprise nigh of the AFSC population express mesenchymal markers CD90, CD166, CD105 simply not CD34, CD45 or pluripotent markers. These cells have been shown to reprogram chop-chop and efficiently past the overexpression of transcription factors OCT3/four, SOX2, KLF4, and c-MYC, which make them an attractive autologous cell source for subsequent apply in disease modeling and regenerative therapies [50–52].

Amniotic fluid–induced pluripotent stem (AF-IPS) cells have been derived using several of the following methods: integrative vector transgene delivery in undefined serum containing feeder-dependent cultures, nonintegrative episomal method in well-defined xeno-free/feeder-gratis cultures, nonintegrating Sendai virus, Piggybac transposon arrangement, and by transgene-free method using histone deacetylase inhibitor valproic acrid (VPA) [49,l,53–55]. Unmarried (Oct4) and two-factor (Oct4 and KLF4) transduction of AFSCs has also been successful in generating IPSCs underscoring the similarity of their epigenetic status to pluripotent cells. Methylation and microarray analyses showed a loftier correlation coefficient betwixt human AF-IPS cells and hESCs and a low correlation coefficient between AF-IPSCs and AFSCs displaying like epigenetic status and gene expression profiles [fifty,52]. Teratoma formation experiments confirmed that AF-IPSCs take the aforementioned differentiation potential as dermal fibroblast-IPS and hESCs. AF is thus ideal for a prenatal harvest to generate and banking company patient-specific IPSCs for autologous treatments, potential allogeneic cellular therapies, pharmaceutical screening, and disease modeling.

The AF-IPSCs can give rise to keratinocytes, hepatocytes, cardiomyocytes, islet cells, neurons, etc and provide a reservoir of cells for congenital anomalies without concerns for immunologic rejection. AF-IPSCs derived from Trisomy 21 patients used in affliction modeling showed impaired neural differentiation [56,57]. AF-IPSCs have been generated from the AFCs of β-thalassemia patients using a single excisable lentiviral cassette [58]. Ma et al. [59] demonstrated that IPSCs derived from AFSCs of β-thalassemia patients could be edited and corrected past transcription activator-similar effector nucleases (TALENs). The cistron-corrected IPSCs from different patients differentiated into erythroblasts expressing normal β-globin. Contempo studies accept demonstrated that hAFCs tin can be differentiated through a pluripotent state into functional cardiomyocytes [threescore,61]. The differentiated cells contracted spontaneously and expressed cardiac Troponin, β-myosin heavy chain. Qin [62] haS demonstrated that microvesicles generated from homo AF-IPSCs repair cerebral ischemia damage in rats. In another report, Kajiwara and colleagues [63] differentiated human AF-IPSCs into keratinocytes and successfully reconstructed a 3-D skin graft in a fetal rat myelomeningocele (MMC) neural tube defect model.

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Fetal Handling of Genetic Disorders

Quoc-Hung Fifty. Nguyen Doctor , ... Tippi C. MacKenzie Physician , in Perinatal Genetics, 2019

Admission to Stem Cell Populations

Similar to the rationales cited in fetal stem jail cell therapy, IUGT has the potential to access stem cell populations during a fourth dimension when they be in college relative frequency to other cells. Usage of viral vectors that integrate into the host genome would allow for pregnant expansion of the viral transgene into daughter cells. An experiment using VSV-1000 pseudotype equine infectious anemia with a transgene for β-galactosidase in mice resulted in multiorgan factor expression that was uniquely plant to be in clusters of cells. This suggested clonal expansions of originally transduced cells. 83 IUGT with lentiviral delivery of lacZ has resulted in transduction of muscle stem cells (satellite cells) in a murine muscular injury model. 84

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Gene AND CELLULAR TRANSPLANTATION THERAPIES FOR HUNTINGTON'Southward DISEASE

SHILPA RAMASWAMY , JEFFREY H. KORDOWER , in CNS Regeneration (2nd Edition), 2008

Alternative Transplantation Studies

Due to the limited availability of embryonic or fetal stem cells for therapy, many researchers are looking into alternative donor sources for transplantation. Such sources of stem cells are derived from umbilical cord claret, bone marrow and developed sources like the subventricular zone and dentate gyrus. In a QA-lesioned rat model of HD, rat bone marrow cells were injected bilaterally into the striatum ( Lescaudron et al., 2003). Animals treated with bone marrow cells showed significant improvements in working retention performance compared to lesioned rats. However, there was no rescue from cell decease in the striatum and less than i% of transplanted cells expressed a neuronal phenotype. Preliminary results in a study using human umbilical cord cells showed that huntingtin transgenic mice receiving transplants had increased survival and decreased weight loss (Ende and Chen, 2001). These results are promising for the employ of umbilical cord claret in Hard disk drive, and farther analysis of histological and symptomatic benefits should be conducted.

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Induced pluripotent stem cells derived from amniotic fluid stalk cells

Ellen Petzendorfer , Pascale V. Guillot , in Prison cell Sources for iPSCs, 2021

Amniotic fluid stem cells

Amniotic fluid stem (AFS) cells are somatic fetal stalk cells which are shed into the amniotic fluid from the fetus ( Hawkins et al., 2017). In humans, hAFS cells tin exist isolated at whatsoever gestational age from the amniotic fluid sampled from 10 weeks of gestation until term. When isolated during the first trimester, hAFS cells are idea to be more than primitive than their counterparts isolated from the amniotic fluid later on during gestation, as that share 82% transcriptome identity with human ES cells. Nonetheless, they are not accessible in the autologous setting. In dissimilarity, mid and late trimester cells are accessible during ongoing pregnancy and maintain relevant therapeutic characteristics, thereby present potential for autologous use (Loukogeorgakis and De Coppi, 2016). AFS cells are multipotent meaning they are capable of forming multiple cells types from one lineage because of beingness multipotent and non pluripotent they do not express the pluripotency markers OCT4A or form teratomas in vivo (Hawkins et al., 2017; Vlahova et al., 2019). AFS cells are nontumorigenic, take immunogenicity, maintain their phenotype and karyotype when expanded in vitro and later on cryopreservation, accept high growth kinetics and a more than primitive phenotype (Guillot., 2015; Loukogeorgakis and De Coppi, 2016; Hawkins et al., 2017). As they are isolated early on in fetal evolution, their level or commitment is depression, making them more amenable to reprogramming. It has been reported that hAFS cells are more speedily and efficiently reprogrammed into iPSCs when compared to developed cells (Slamecka et al., 2016). These reprogrammed cells have a potential use for both regenerative medicine by using lineages derived from iPSC that are otherwise not accessible and for disease modeling (Slamecka et al., 2016).

AFS cells accept been reprogrammed to pluripotency using serval different methods including; viral integrative, viral nonintegrative, chemic reprogramming, and episomal reprogramming (Fig. 1.three).

Figure ane.3. The iv methods which have been used to reprogram AFS cells to pluripotency. (one) Transduction of transcription factors via integrating viruses. (2) Transduction of transcription factors using viral nonintegrating vectors. (3) Episomal reprogramming. (4) Chemic reprogramming using valproic acid.

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