Murine Tissue-Engineered Stomach Demonstrates Epithelial Differentiation

Speer, Allison L.; Sala, F.G.; Matthews, Janice R.; Grikscheit, Tracy C.

doi:10.1016/j.jss.2011.03.062

Cited by 48 publications

(30 citation statements)

References 39 publications

(59 reference statements)

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“…49 To assess this study's generalizability, future experiments will explore the potential of neurosphere supplementation in TEC derived from aganglionic colon of various etiologies. Moreover, tissue-engineered esophagus, 50,51 stomach, 52,53 and small intestine 32,53-55 have been formed in highly similar protocols to the process employed to form TEC, and neurosphere supplementation for enteric neuropathies involving each of these tissue-engineered structures remains to be explored. Because these neurons participate in complex physiological processes, further work is required to optimize ENS organization in TEC, assess motor function, identify the reproduction of neuronal reflex pathways, and evaluate proper interfacing of secretomotor and vasomotor neurons with the epithelium and vasculature.…”

Section: Discussionmentioning

confidence: 99%

Human and Murine Tissue-Engineered Colon Exhibit Diverse Neuronal Subtypes and Can Be Populated by Enteric Nervous System Progenitor Cells When Donor Colon Is Aganglionic

Wieck

El‐Nachef

Hou

et al. 2016

Tissue Engineering Part A

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Purpose: Tissue-engineered colon (TEC) might potentially replace absent or injured large intestine, but the enteric nervous system (ENS), a key component, has not been investigated. In various enteric neuropathic diseases in which the TEC is derived from aganglionic donor colon, the resulting construct might also be aganglionic, limiting tissue engineering applications in conditions such as Hirschsprung disease (HD). We hypothesized that TEC might contain a diverse population of enteric neuronal subtypes, and that aganglionic TEC can be populated by neurons and glia when supplemented with ENS progenitor cells in the form of neurospheres. Materials and Methods: Human and murine organoid units (OU) and multicellular clusters containing epithelium and mesenchyme were isolated from both mouse and human donor tissues, including from normally innervated and aganglionic colon. The OU were seeded onto a biodegradable scaffold and implanted within a host mouse, resulting in the growth of TEC. Aganglionic murine and human OU were supplemented with cultured neurospheres to populate the absent ENS not provided by the OU to rescue the HD phenotype. Results: TEC demonstrated abundant smooth muscle and clusters of neurons and glia beneath the epithelium and deeper within the mesenchyme. Motor and afferent neuronal subtypes were identified in TEC. Aganglionic OU formed TEC with absent neural elements, but neurons and glia were abundant when aganglionic OU were supplemented with ENS progenitor cells. Conclusion: Murine and human TEC contain key components of the ENS that were not previously identified, including glia, neurons, and fundamental neuronal subtypes. TEC derived from aganglionic colon can be populated with neurons and glia when supplemented with neurospheres. Combining tissue engineering and cellular replacement therapies represents a new strategy for treating enteric neuropathies, particularly HD.

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Section: Discussionmentioning

confidence: 99%

Human and Murine Tissue-Engineered Colon Exhibit Diverse Neuronal Subtypes and Can Be Populated by Enteric Nervous System Progenitor Cells When Donor Colon Is Aganglionic

Wieck

El‐Nachef

Hou

et al. 2016

Tissue Engineering Part A

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“…These were seeded and successfully replaced the small bowel in rodent, swine, and canine model recipients [47][48][49]. In addition to small bowel, the esophagus, stomach, large bowel, and anal sphincters have also been engineered utilizing similar strategies [13,37,[50][51][52][53][54][55].…”

Section: Intestinementioning

confidence: 99%

Whole-Organ Tissue Engineering: No Longer Just a Dream

Wrenn

Weiss

2016

Curr Pathobiol Rep

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Purpose of Review The true potential of the field of transplant surgery remains limited due to shortages of available transplantable allografts and, following transplantation, acute and chronic rejection with need for lifelong immune suppression. An alternative approach is to bioengineer organs to be utilized in vivo, replacing diseased or malfunctioning human organs. This revolutionary step in medicine could have virtually unlimited therapeutic potential. Recent Findings Multiple strategies have been used to replicate functional transplantable organs without deleterious host immune response. Common approaches include the use of decellularized tissue scaffolds and of 3D bioprinting. Continuing challenges include engraftment and maturation of recipient cells, and long-term tissue viability and function. Summary We will review in brief the history of the field and the progress to date with multiple organ systems, highlighting our personal experience in lung regeneration. Finally, we will discuss the challenges that lie ahead to reach the dream of fully functional and transplantable bioengineered organs.

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“…7 Our efficiency with murine esophagus is similar (when accounting for the smaller sample size) to our results in murine TESI (89% of harvested implants, 39 out of 44) 12 while tissue-engineered stomach appears to be less successful (50%, 15 out of 30, harvested implants). 13 Although variable in percentage, the successful tissue engineering of multiple gastrointestinal segments on the same biomaterial highlights its versatility for several progenitor cell populations. This tissue engineering technique is simple and requires only one cell source, EOU, for all of the donor cells (epithelial, fibroblasts, smooth muscle, and nerve cells), unlike other more complex models 2,3,5,6,28,30,36,37 that require cells from numerous sites or even different animals.…”

Section: Ck13mentioning

confidence: 99%

“…7 However, to investigate the regenerative mechanisms underpinning the tissue generation, we recently transitioned to the mouse model, which necessitated redesigning the scaffold for the smaller size of the recipient. Both tissue-engineered small intestine (TESI) 12 and stomach 13 were generated by this approach in the mouse. However, the esophagus has several key differences from the rest of the gastrointestinal tract.…”

Section: Introductionmentioning

confidence: 99%

Murine and Human Tissue-Engineered Esophagus Form from Sufficient Stem/Progenitor Cells and Do Not Require Microdesigned Biomaterials

Spurrier

Speer

Hou

et al. 2015

Tissue Engineering Part A

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Purpose: Tissue-engineered esophagus (TEE) may serve as a therapeutic replacement for absent foregut. Most prior esophagus studies have favored microdesigned biomaterials and yielded epithelial growth alone. None have generated human TEE with mesenchymal components. We hypothesized that sufficient progenitor cells might only require basic support for successful generation of murine and human TEE. Materials and Methods: Esophageal organoid units (EOUs) were isolated from murine or human esophagi and implanted on a polyglycolic acid/poly-l-lactic acid collagen-coated scaffold in adult allogeneic or immunedeficient mice. Alternatively, EOU were cultured for 10 days in vitro prior to implantation. Results: TEE recapitulated all key components of native esophagus with an epithelium and subjacent muscularis. Differentiated suprabasal and proliferative basal layers of esophageal epithelium, muscle, and nerve were identified. Lineage tracing demonstrated that multiple EOU could contribute to the epithelium and mesenchyme of a single TEE. Cultured murine EOU grew as an expanding sphere of proliferative basal cells on a neuromuscular network that demonstrated spontaneous peristalsis in culture. Subsequently, cultured EOU generated TEE. Conclusions: TEE forms after transplantation of mouse and human organ-specific stem/progenitor cells in vivo on a relatively simple biodegradable scaffold. This is a first step toward future human therapies.

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Murine Tissue-Engineered Stomach Demonstrates Epithelial Differentiation

Cited by 48 publications

References 39 publications

Human and Murine Tissue-Engineered Colon Exhibit Diverse Neuronal Subtypes and Can Be Populated by Enteric Nervous System Progenitor Cells When Donor Colon Is Aganglionic

Human and Murine Tissue-Engineered Colon Exhibit Diverse Neuronal Subtypes and Can Be Populated by Enteric Nervous System Progenitor Cells When Donor Colon Is Aganglionic

Whole-Organ Tissue Engineering: No Longer Just a Dream

Murine and Human Tissue-Engineered Esophagus Form from Sufficient Stem/Progenitor Cells and Do Not Require Microdesigned Biomaterials

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