Anatomy - lecture 12 - Recreating Anatomy

Key Topics Covered

  • Key Properties of Stem Cells

  • Cell-Cell Communication: Niche & Microenvironment

  • Applications of Stem Cells in Regenerative Medicine

    • Self-organization vs. Guided Engineering Approaches

    • Example 1: Intestinal Organoids and Engineering the Niche

    • Example 2: Bioengineering Pancreatic Cell Niche(s)

Overview on Stem Cells

Definition and Properties

  • Stem Cells: Undifferentiated cells with the ability to self-renew and differentiate into specialized cells

  • Functionality: Contribute to organ formation, replace damaged or dead cells, and maintain the stem cell pool for tissue demand

Types of Stem Cells

  1. Embryonic Stem Cells (ESCs)

    • Origin: Inner cell mass of the blastocyst

    • Characteristics: Self-renewal, pluripotent (capable of becoming any cell type)

    • From implantation stage

  2. Adult Stem Cells (ASCs)

    • An undufferentiated cell found in some adult organs which can self-renew and differentiate to become most or all the specialized cell types within the specific organ

    • Generation: Created during ontogeny; exist in adult tissues

    • Characteristics: Self-renewal, multipotent (can differentiate into a limited range of cells)

    • Limited number of organs and can be unipotent

  3. Induced Pluripotent Stem Cells (iPSCs)

    • Mature, differentiated cells can be reprogrammed to become pluripotent

    • Source: Derived from somatic (adult) cells via reprogramming factors (e.g., Oct4, Sox2)

    • Applications: Patient-specific cells for research and therapy

Mechanisms of Cell Identity Establishment

  • Processes involved include transcriptional regulation, chromatin modification, and extrinsic signaling (e.g., growth factors)

  • Transcriptional and chromatin program has intrinsic factors

  • Extrinsic signals maintain stem cells in the multipotent state

Stem Cell Niche & Microenvironment

Niche Concept

  • Cellular Niche: A specialized microenvironment that influences stem cell behavior through interactions with both supporting cells and the extracellular matrix (ECM)

  • Functionality of Niche: Supports self-renewal, regulated proliferation, and differentiation of stem cells

    • Also keep stem cell potent

Intestinal Stem Cell Niche

  • Includes various cell types such as goblet cells, enteroendocrine cells, and Paneth cells

  • Crucial for maintaining cell turnover and intestinal health (5-day turnover)

  • Intestinal stem cell niche is in the bottom of microvili

Applications in Regenerative Medicine

Pluripotent Stem Cell Applications

  • Cell Therapy for:

    • Liver diseases

    • Diabetes (Pancreatic B-cells)

    • Cystic Fibrosis (Airway cells)

Disease Modeling

  • Investigating genetic disorders and infectious diseases using organoids and patient-specific iPSCs for drug screening and toxicity testing

Recreating Anatomy: Methodologies

  • Two main steps in bioengineering:

    • Reading: components, ratios, and spatial distribution - tissue architecture

    • Writing: assembling, maturation, and preservation

Key Components in Tissue Engineering

  1. Components (e.g., cells, ECM)

  2. Ratios (cell types in the tissue)

  3. Spatial Distribution (tissue architecture)

  4. Assembling and Maturation

  5. Preservation Techniques

Organoid Technology

  • Definition: Miniaturized self-organizing 3D cultures derived from stem cells, mimicking organ function

  • Applications: Studying development and function of various organs, such as gastrointestinal system and pancreas

  • Self organization: process by which local interactions between cells that are initially disordered lead to the emergence of patterns and functions

    • Self-assembly: time-evolving controlof relative cell positions

    • Self-patterning: spatiotemporal control of cell status

    • Self-driven morphogenesis: spatiotemporalcontrol of intrinsic tissue mechanics

  • Intestinal organoids: engineering cell-ECM interactions → engineering size and geometry → organoid assembly → organogenesis by design

Engineering the Pancreatic Niche

  • Pancreas lack regenerative properties so pancreatic cancer is basically incurable

  • Understanding developmental biology to engineer pancreatic cells using factors like FGF10, RA, and Notch

  • Focus on building functional pancreatic tissue through encapsulation strategies and bioprinting approaches

  • Limitation - struggle to produce mature beta cells

  • Guided engineering produces a better, more functional product