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Anthony Atala

Publications and source records attributed to Anthony Atala.

At least 19 recordsLinked to original sources
PubMed2026

Using Organoids to Unlock the Potential of Human Torpor for Spaceflight.

PURPOSE OF REVIEW: This paper reviews the current understanding of the potential for humans to enter a state of torpor/hibernation, and discusses the possibility of inducing torpor in astronauts for long-duration space travel, including some of the physiological, technological, and ethical considerations associated with its implementation. By exploring means to induce torpor in various human organoid systems, we hope such research can provides insights to comprehensive solutions to overcome some of the major hurdles that limit the potential for human to enter a state of torpor during long-duration deep-space missions, and contribute to the ongoing efforts to make such missions more feasible and safer for astronauts. RECENT FINDINGS: On future deep space missions such as NASA's planned missions to the Moon, Mars, and near-Earth asteroids, astronauts will be continuously exposed to environments that are radically different from those on Earth, each presenting multiple logistical and physiological challenges. Beyond the well-documented physiological effects of microgravity, space travelers will encounter a complex radiation environment that may contribute to significant short- and long-term adverse effects on human physiology and increase the risk of cancer and other diseases. Besides these physical challenges, life support systems must also be designed to mitigate psychological impacts of long-term isolation and confinement - all of which collectively pose formidable engineering problems. Hibernation/torpor is a state of prolonged inactivity and metabolic depression used by a wide variety of mammals to survive periods of cold temperatures and food scarcity, including some primates and perhaps even an extinct early line of hominins that lived nearly half a million years ago. Since modern humans share common ancestry with these hominins and hibernating primates, it is likely the human genome encodes the necessary genetic information to hibernate, or at least enter the similar, more transient state of torpor. The reduced body activity, lowered metabolism, and decreased energy requirements that characterize torpor suggest that developing means of inducing such a state in astronauts could address these challenges, including providing a degree of radioprotection. SUMMARY: This review explores the potential application of human torpor as a countermeasure to address the many challenges posed by long-duration spaceflight beyond low-Earth orbit (LEO), discusses various natural hibernating model systems for studying means of inducing a torpor-like state in humans, and highlights the vast potential of using human organoids to test and validate mechanisms that govern induction and maintenance of torpor to identify the means to one day safely induce this state in astronauts to provide additional protection from the myriad stressors of spaceflight.

Astronaut Health↗
PubMed2022

Organoids and microphysiological systems: Promising models for accelerating AAV gene therapy studies.

The FDA has predicted that at least 10-20 gene therapy products will be approved by 2025. The surge in the development of such therapies can be attributed to the advent of safe and effective gene delivery vectors such as adeno-associated virus (AAV). The enormous potential of AAV has been demonstrated by its use in over 100 clinical trials and the FDA's approval of two AAV-based gene therapy products. Despite its demonstrated success in some clinical settings, AAV-based gene therapy is still plagued by issues related to host immunity, and recent studies have suggested that AAV vectors may actually integrate into the host cell genome, raising concerns over the potential for genotoxicity. To better understand these issues and develop means to overcome them, preclinical model systems that accurately recapitulate human physiology are needed. The objective of this review is to provide a brief overview of AAV gene therapy and its current hurdles, to discuss how 3D organoids, microphysiological systems, and body-on-a-chip platforms could serve as powerful models that could be adopted in the preclinical stage, and to provide some examples of the successful application of these models to answer critical questions regarding AAV biology and toxicity that could not have been answered using current animal models. Finally, technical considerations while adopting these models to study AAV gene therapy are also discussed.

Animals↗
PubMed2007

Isolation of amniotic stem cell lines with potential for therapy.

Stem cells capable of differentiating to multiple lineages may be valuable for therapy. We report the isolation of human and rodent amniotic fluid-derived stem (AFS) cells that express embryonic and adult stem cell markers. Undifferentiated AFS cells expand extensively without feeders, double in 36 h and are not tumorigenic. Lines maintained for over 250 population doublings retained long telomeres and a normal karyotype. AFS cells are broadly multipotent. Clonal human lines verified by retroviral marking were induced to differentiate into cell types representing each embryonic germ layer, including cells of adipogenic, osteogenic, myogenic, endothelial, neuronal and hepatic lineages. Examples of differentiated cells derived from human AFS cells and displaying specialized functions include neuronal lineage cells secreting the neurotransmitter L-glutamate or expressing G-protein-gated inwardly rectifying potassium channels, hepatic lineage cells producing urea, and osteogenic lineage cells forming tissue-engineered bone.

Amniotic Fluid↗
PubMed2007

Amniotic fluid and bone marrow derived mesenchymal stem cells can be converted to smooth muscle cells in the cryo-injured rat bladder and prevent compensatory hypertrophy of surviving smooth muscle cells.

PURPOSE: Wound healing of the cryo-injured bladder can bring about organ remodeling because of incomplete reconstitution of depleted smooth muscle cells. Stem cell transplantation could be beneficial to improve smooth muscle cell regeneration and/or modulate the remodeling process. The repair of bladder injury using adult-type stem cells would be useful for adult urological patients but unsuited for neonatal patients, in whom major benefits are likely to derive from fetal-type stem cells. MATERIALS AND METHODS: The smooth muscle cell differentiation potential of fetal-type vs adult-type stem cells was evaluated by injecting green fluorescent protein labeled mesenchymal stem cells from rat amniotic fluid or bone marrow, respectively, in cryo-injured rat bladder walls. RESULTS: At 30 days after transplantation only a few fetal-type or adult-type mesenchymal stem cells gave rise to enteric or vascular smooth muscle cells, whereas most mesenchymal stem cells appeared incapable of specific differentiation. In vitro co-culture experiments of smooth muscle cells with fetal-type or adult-type mesenchymal stem cells selectively labeled with distinct fluorochromes showed the presence of hybrid cells, suggesting that some mesenchymal stem cells can undergo cell fusion. Surprisingly the major effect of rat bone marrow or amniotic fluid mesenchymal stem cell transplantation seemed to be preventing cryo-injury induced hypertrophy of surviving smooth muscle cells. CONCLUSIONS: In this model stem cell transplantation has a limited effect on smooth muscle cell regeneration. Instead it can regulate post-injury bladder remodeling, possibly via a paracrine mechanism.

Amniotic Fluid↗
PubMed2006

Carbon nanotube applications for tissue engineering.

As the field of tissue engineering advances, new tools for better monitoring and evaluating of engineered tissues along with new biomaterials to direct tissue growth are needed. Carbon nanotubes may be an important tissue engineering material for improved tracking of cells, sensing of microenvironments, delivering of transfection agents, and scaffolding for incorporating with the host's body. Using carbon nanotubes for optical, magnetic resonance and radiotracer contrast agents would provide better means of evaluating tissue formation. In addition, monitoring and altering intra and intercellular processes would be useful for design of better engineered tissues. Carbon nanotubes can also be incorporated into scaffolds providing structural reinforcement as well as imparting novel properties such as electrical conductivity into the scaffolds may aid in directing cell growth. Potential cytotoxic effects associated with carbon nanotubes may be mitigated by chemically functionalizing the surface. Overall, carbon nanotubes may play an integral role as unique biomaterial for creating and monitoring engineered tissue.

Animals↗
PubMed2006

Tissue-engineered autologous bladders for patients needing cystoplasty.

BACKGROUND: Patients with end-stage bladder disease can be treated with cystoplasty using gastrointestinal segments. The presence of such segments in the urinary tract has been associated with many complications. We explored an alternative approach using autologous engineered bladder tissues for reconstruction. METHODS: Seven patients with myelomeningocele, aged 4-19 years, with high-pressure or poorly compliant bladders, were identified as candidates for cystoplasty. A bladder biopsy was obtained from each patient. Urothelial and muscle cells were grown in culture, and seeded on a biodegradable bladder-shaped scaffold made of collagen, or a composite of collagen and polyglycolic acid. About 7 weeks after the biopsy, the autologous engineered bladder constructs were used for reconstruction and implanted either with or without an omental wrap. Serial urodynamics, cystograms, ultrasounds, bladder biopsies, and serum analyses were done. RESULTS: Follow-up range was 22-61 months (mean 46 months). Post-operatively, the mean bladder leak point pressure decrease at capacity, and the volume and compliance increase was greatest in the composite engineered bladders with an omental wrap (56%, 1.58-fold, and 2.79-fold, respectively). Bowel function returned promptly after surgery. No metabolic consequences were noted, urinary calculi did not form, mucus production was normal, and renal function was preserved. The engineered bladder biopsies showed an adequate structural architecture and phenotype. CONCLUSIONS: Engineered bladder tissues, created with autologous cells seeded on collagen-polyglycolic acid scaffolds, and wrapped in omentum after implantation, can be used in patients who need cystoplasty.

Adolescent↗
PubMed2006

In vitro evaluation of a poly(lactide-co-glycolide)-collagen composite scaffold for bone regeneration.

Numerous materials have been proposed for bone tissue regeneration. However, none has been shown to be entirely satisfactory. In this study we fabricated a hybrid composite scaffold composed of poly(D,L-lactide-co-glycolide) (PLGA) and a naturally derived collagen matrix derived from porcine bladder submucosa matrix (BSM), and evaluated the biological activities and physical properties of the scaffold for use in bone tissue regeneration. The BSM-PLGA composite scaffolds are able to promote cellular interactions and possess uniformly interconnected pores with adequate structural integrity. The composite scaffolds were tested with both human embryonic stem (hES) cells and bovine osteoblasts (bOB). Cells seeded on the composite scaffolds readily attached, infiltrated and proliferated, as confirmed by cell viability and mitochondrial metabolic activity. Use of the composite scaffolding system with cells may enhance the formation of bone tissue for therapeutic regeneration.

Animals↗
PubMed2006

Mesenchymal stem cells and adipogenesis in hemangioma involution.

Hemangioma is a benign tumor of infancy whose hallmark is rapid growth during the first year of life followed by slow regression during early childhood. The proliferating phase is characterized by abundant immature endothelial cells, the involuting phase by prominent endothelial-lined vascular channels and endothelial apoptosis, and the involuted phase by few remaining capillary-like vessels surrounded by loose fibrofatty tissue. Nothing is known about the mechanisms that contribute to the adipogenesis during this spontaneous regression. We postulated that mesenchymal stem cells (MSCs) reside in the tumor and preferentially differentiate into adipocytes. To test this hypothesis, we isolated MSCs from 14 proliferating and five involuting hemangiomas by taking advantage of the well known selective adhesion of MSCs to bacteriologic dishes. These hemangioma-derived MSCs (Hem-MSCs) are similar to MSCs obtained from human bone marrow, expressing the cell surface markers SH2 (CD105), SH3, SH4, CD90, CD29, smooth muscle alpha-actin, and CD133 but not the hematopoietic markers CD45 and CD14 or the hematopoietic/endothelial markers CD34, CD31, and kinase insert domain receptor (KDR). Hem-MSCs exhibited multilineage differentiation with robust adipogenic potential that correlated with the proliferating phase. The numbers of adipogenic Hem-MSCs were higher in proliferating-phase than in involuting-phase tumors and higher than in normal infantile skin. Furthermore, Hem-MSCs exhibited a random pattern of X-chromosomal inactivation, indicating that these cells are not clonally derived. In summary, we have identified MSCs as a novel cellular constituent in infantile hemangioma. These MSCs may contribute to the adipogenesis during hemangioma involution.

Adipogenesis↗
PubMed2006

Recent advances in the field of urology.

Advances have been made in every aspect of urology that strengthen the scientific underpinning of current urologic practices and that hopefully will encourage further scientific investigation into the source, mechanisms, and cure of urologic diseases. This article reviews some of the advances that have been detailed in the recent urologic literature.

Female Urogenital Diseases↗
PubMed2006

Amniotic fluid and placental stem cells.

Human amniotic fluid has been used in prenatal diagnosis for more than 70 years. It has proven to be a safe, reliable, and simple screening tool for a wide variety of developmental and genetic diseases. However, there is now evidence that amniotic fluid may have more use than only as a diagnostic tool and may be the source of a powerful therapy for a multitude of congenital and adult disorders. A subset of cells found in amniotic fluid and placenta has been isolated and found to be capable of maintaining prolonged undifferentiated proliferation as well as able to differentiate into multiple tissue types encompassing the three germ layers. It is possible that in the near future, we will see the development of therapies using progenitor cells isolated from amniotic fluid and placenta for the treatment of newborns with congenital malformations as well as of adults, using cryopreserved amniotic fluid and placental stem cells. In this chapter, we describe a number of experiments that have isolated and characterized pluripotent progenitor cells from amniotic fluid and placenta. We also discuss various cell lines derived from amniotic fluid and placenta and future directions for this area of research.

Adult Stem Cells↗
PubMed2006

GeneChips in stem cell research.

An understanding of the genes and signaling networks responsible for stem cell growth and differentiation will be essential for their ultimate therapeutic application. GeneChips are miniature platforms of nucleotides capable of monitoring the expression levels of almost every known and unknown gene. Performing a GeneChip experiment is like snapping a picture of a cell's mRNA (transcripts), thus giving a static view and measurement of gene expression inside the cell. Taking multiple "pictures" of stem cells as they grow and differentiate will provide insight into the genetic mechanisms of "stemness" or can be used to create "transcriptional signatures" to assess differentiation and variability between stem cell lines. The first half of this chapter covers the many components involved in a GeneChip experiment, illustrating the many variables at each step and describing a protocol for analysis that is inexpensive and requires minimal computer skills. The chapter then describes how researchers are currently applying GeneChips to stem cell biology. We conclude that the true potential of GeneChip technology lies in the in silico analysis-their integration and comparison of diverse data sets, where the biological questions are the driving force in the analysis.

Animals↗
PubMed2006

Tissue engineering using adult stem cells.

Patients with a variety of diseases may be treated with transplanted tissues and organs. However, there is a shortage of donor tissues and organs, which is worsening yearly because of the aging population. Scientists in the field of tissue engineering are applying the principles of cell transplantation, material science, and bioengineering to construct biological substitutes that will restore and maintain normal function in diseased and injured tissues. The stem cell field is also advancing rapidly, opening new options for cellular therapy and tissue engineering. The use of adult stem cells for tissue engineering applications is promising. This chapter discusses applications of these new technologies for the engineering of tissues and organs. The first part provides an overview of regenerative medicine and tissue engineering techniques; the second highlights different adult stem cell populations used for tissue regeneration.

Adult Stem Cells↗
PubMed2006

Engineering of blood vessels from acellular collagen matrices coated with human endothelial cells.

Small-caliber synthetic grafts used for coronary bypass artery grafting are compromised by thrombogenicity and accelerated intimal thickening, resulting in early graft occlusion. Herein we describe the fabrication and physical properties of small-caliber blood vessels using decellularized porcine aortic segments. These vessels were further coated with human saphenous vein endothelial cells (HSVECs) for future clinical applications. Chemical staining of decellularized vessels showed that they preserved their native matrix architecture, including several collagen layers in between internal and external elastin layers. The burst pressure for the decellularized vessels was higher than 1,000 mmHg. HSVECs, seeded on the luminal side, adhered to the matrix and formed a uniform monolayer. HSVEC-seeded vessels produced prostaglandin I2 and released vasoactive agents in response to the calcium ionophore A23187. These results show that engineered blood vessels coated with the host endothelial cells possess morphologic and functional characteristics of human small-caliber vessels. Tissue-engineered vessels may potentially be useful clinically as vascular grafts.

Animals↗
PubMed2006

Recent developments in tissue engineering and regenerative medicine.

PURPOSE OF REVIEW: Currently, patients suffering from diseased and injured organs are treated with transplanted organs or cells. There is, however, a severe shortage of donor tissues and organs that is worsening yearly given the aging population. This paper reviews recent advances that have occurred in regenerative medicine and describes applications of new technologies to treat diseased or damaged organs and tissues. RECENT FINDINGS: Most current strategies for tissue engineering depend upon a sample of autologous cells from the diseased organ of the patient. Biopsies from patients with extensive end-stage organ failure, however, may not yield enough normal cells. In these situations, stem cells are envisioned as being an alternative source. Stem cells can be derived from discarded human embryos (human embryonic stem cells), from fetal tissue or from adult sources (bone marrow, fat, skin). Therapeutic cloning offers a potentially limitless source of cells for tissue engineering applications. SUMMARY: Increasingly, scientists in the fields of regenerative medicine and tissue engineering have applied the principles of cell transplantation, material science and bioengineering to construct biological substitutes that will restore and maintain normal function in diseased and injured tissues.

Animals↗
PubMed2006

Recent applications of regenerative medicine to urologic structures and related tissues.

PURPOSE OF REVIEW: A severe shortage of donor tissues and organs exists, which is worsening yearly given the aging population. Currently, patients suffering from diseased and injured organs are treated with transplanted organs or cells. This paper reviews recent advances that have occurred in regenerative medicine and describes application of new technologies to treat diseased or damaged organs and tissues. RECENT FINDINGS: Although most current strategies for tissue engineering depend upon a sample of autologous cells from the diseased organ of the patient, biopsies from patients with extensive end-stage organ failure may not yield enough normal cells. In these situations, stem cells are envisioned as being an alternative source. Stem cells can be derived from discarded human embryos (human embryonic stem cells), from fetal tissue, or from adult sources (bone marrow, fat, skin). Therapeutic cloning offers a potentially limitless source of cells for tissue engineering applications. SUMMARY: Recently, scientists in the fields of regenerative medicine and tissue engineering have applied the principles of cell transplantation, material science, and bioengineering to construct biological substitutes that will restore and maintain normal function in diseased and injured tissues.

Animals↗
PubMed2005

Controlled fabrication of a biological vascular substitute.

Autologous and synthetic vessel grafts have been used as a vascular substitute for cardiovascular bypass procedures. However, these materials are limited by the availability of appropriate caliber autologous vessels, increased susceptibility to thrombosis and intimal hyperplasia following surgery. Electrospinning technology offers the potential for controlling composition, structure and mechanical properties of biomaterials. Vascular graft scaffolds have been fabricated using electrospun polymer blends of Type I collagen, elastin from ligamentum nuchae, and poly (d,l-lactide-co-glycolide). This study demonstrates improved electrospinning characteristics versus previous studies by increasing polymer concentration and adding PLGA to the polymer blend. Additionally, new in vitro biocompatibility and mechanical testing data is presented. The scaffolds possess tissue composition and mechanical properties similar to native vessels. The electrospun vessel matrix is biocompatible and does not elicit local or systemic toxic effects when implanted in vivo. This study demonstrates the promise of electrospinning as a fabrication process for a functional vascular graft for clinical use.

Animals↗
PubMed2005

Failure of differentiation into mature myotubes by muscle precursor cells with the side-population phenotype after injection into irreversibly damaged striated urethral sphincter.

We previously showed that the injection of a heterogeneous population of muscle precursor cells (MPCs) into striated urethral sphincter irreversibly damaged by electrocoagulation results in the formation of functional myotubes. To gain further insights into the role played by the different types of MPCs, we elected to sort the MPCs by Hoechst 33342 staining/fluorescence-activated cell-sorter analysis before injection. We found that the side population (SP) cells (muscle stem cells) injected in isolation survived, whereas the main population (MP) cells did not. However, the SP cells failed to differentiate into mature myotubes, as observed previously with unfractionated MPCs containing both SP and MP cells. This result suggests that interactions between SP and MP cells are required for the formation of myotubes in a nonregenerating muscle. In the setting of sphincter insufficiency, injection of MPCs at different stages of maturation may be a better option than purified muscle stem cells.

Animals↗