Stem Cell Therapy

Stem cells are biological cells found in all multicellular organisms, that can divide (through mitosis) and differentiate into diverse specialized cell types and can self-renew to produce more stem cells.

PRIMARY SOURCES OF STEM CELLS

I.   Embryonic Stem Cells: Derived from very early embryo, which are  isolated  from the  inner  cell mass  of  blastocysts

II.  Fetal Stem Cells: Collected from fetal tissue at a somewhat later stage of  development.      

III. Adult Stem Cells: Obtained from mature tissues, differentiate into narrow range of cell types.

Source : Bone marrow, Adipose tissue, which requires extraction by liposuction

  • Blood, which requires extraction through pheresis, wherein blood is drawn from the donor (similar to a blood donation), passed through a machine that extracts the stem cells and returns other portions of the blood to the donor.

The  classical  definition  of  a  stem  cell  requires  that  it  possess  two  properties

  • Self –Renewal and Potency
  • SELF – RENEWAL: Ability to renew themselves through mitotic cell division.
  • POTENCY: Capacity to differentiate into specialized cell types.
  • TOTIPOTENT: can differentiate into embryonic   & extraembryonic cell types.
  •  PLURIPOTENT: can differentiate into NEARLY all cells types.
  •  MULTIPOTENT: can differentiate into cells of a CLOSELY RELATED FAMILY.
  •  OLIGOPOTENT: can differentiate into ONLY A FEW CELLS.
  •  UNIPOTENT: can divide into ONLY ONE CELL TYPE ,their own.

Autologous – Stem Cells

  • Sources of the patient’s own stem cells (autologous) are either the cells from patient’s own body or his or her cord blood. For autologous transplants physicians now usually collect stem cells from the peripheral blood rather than the marrow

Allogeneic – Stem Cells

  • Sources of stem cells from another donor (allogeneic) are primarily relatives (familial-allogeneic) or completely unrelated donors (unrelated-allogeneic). The stem cells in this situation are extracted from either the donor’s body or cord blood

How stem cell therapy works?

When stem cells are transplanted into the body and arrive into the injured part, brain being targeted for tissue regeneration, the stem cells are coming in contact with growth chemical’s (like EGF’s , NGF’s and HGF’s )in the body. These chemicals program the stem cells to differentitate into the tissue surrounding it.

Uses:

Drug Testing

  • Stem cells could allow scientists to test new drugs using human cell line which could speed up new drug development.
  • Only drugs that were safe and had beneficial effects in cell line testing would graduate to whole animal or human testing.
  • It would allow quicker and safer development of new drugs.

Any disease in which there is tissue degeneration can be a potential candidate for stem cell therapies


Hematopoietic stem cell transplantation (“HSCT”)

  • Stem cells that give rise to the lymphocytes and other cells of the immune system, also make blood cells, are called hematopoietic stem cells.
  • HSC’s are characterized by the presence of CD 34 antigen
  • The process of taking stem cells from one person and putting them into another is therefore called “ HCST”
  • To treat cancer patients with conditions such as leukemia and lymphoma, sickle cell anaemia,
  • Used in Providing a functional immune system in a person with SCID.
  • In Restoring the haematopoietic system

STEM CELLS IN NEUROLOGY

Many  nervous  system  diseases result  from  loss  of  nerve cells;

  • In Parkinson’s  disease, nerve  cells  that  make the chemical  dopamine die.
  • In  amyotrophic  lateral  sclerosis, the motor  nerve  cells that activate muscles  die.
  • In multiple sclerosis, glia, the cells that  protect  nerve  fibers  are lost.

STEM CELLS IN CARDIOLOGY

  • Cardiovascular disease can deprive heart tissue of oxygen, thereby killing cardiac muscle cells (cardiomyocytes).
  • A cascade of detrimental effects.
  • Eventual heart failure & death
  • Restoring damaged heart muscle tissue, through repair or regeneration, is therefore a potentially new strategy to treat heart failure.

STEM CELLS IN ENDOCRINOLOGY

Type I DM

  • An  autoimmune  disease
  • Characterized  by  destruction  of  pancreatic  beta cells; 80%  of  beta  cells have  to  be destroyed for clinically-evident  diabetes.
  • Human embryonic stem cells  may be grown in cell cultures and stimulate to form insulin-producing cells , that can be transplanted into the patient

STEM CELL THERAPY IN ONCOLOGY

  • Using iPSC derived tissue to repair or replace tissues that have been injured by radiation, chemotherapy or the surgical treatment necessary to treat tumors.

Limbal stem Cell therapy

  • The treatment is known as limbal stem cell therapy, and the patients who received the treatment suffered from chemical burn or genetic disease know as aniridia
  • By replacing the limbal stem cells, the cornea begins to clear up as the cells are replaced with the healthy transparent layer again.

Corneal disease / blindness

  • Take stem cells from healthy eye
  • Grown onto contact lenses in clinical lab
  • Lenses are worn by the patient for a period of three weeks
  • Then migration of human stem cells from lens to damaged eye and begin to repair process
  • Thus heals the damaged cornea and quickly improves the vision

Stem cells in treating baldness

  • As hair follicles contain stem cells – dermal papilla
  • Take stem cells from existing hair follicles
  • Multiply them in cultures
  • Implant the new follicles into the scalp

List of FDA Approved Products

1.HEMACORD (hematopoietic progenitor cells, cord blood) –NYCBB

2.Autologous Cultured chondrocytes–Carticel à

–Repair articular cartilage injuries in the knee of adults who had inadequate/poor response to prior arthroscopic or other surgical repair procedure

–Implanted by a surgical procedure called autologous chondrocyte implantation

3.Autologous Cellular Immunotherapy—Provenge à

–Autologous cellular immunotherapy for the treatment of asymptomatic or minimally symptomatic metastatic castrate resistant (hormone refractory) prostate cancer

Laviv –Fibrocell Technologies (autologous cultured fibroblasts)

–Only personalized cell therapy approved by the FDA for aesthetic use and was recently approved for the improvement of the appearance of moderate-to-severe “smile line” wrinkles (nasolabial folds)

Gintuit–Allogeneic cultured keratinocytes & fibroblasts in Bovine Collagen

–Allogeneic cellularized scaffold product indicated for topical (non-submerged) application to a surgically created vascular wound bed in the treatment of mucogingival conditions in adults

–used as one application over a surgically created vascular wound bed in the oral cavity

Apligraf-Cell based device-Organogenesis

–Indicated for use with standard therapeutic compression for the treatment of non-infected partial and full-thickness skin ulcers due to venous insufficiency of greater than 1 month duration and which have not adequately responded to conventional ulcer therapy

.Dermagraft-cell based device -Advanced  Biohealing

–cryopreserved human fibroblast–derived dermal substitute. Made from human cells known as fibroblasts, placed on a dissolvable mesh material

–Indicated for full-thickness diabetic foot ulcers that have been present for longer than 6 weeks.

PRIMARY CHALLENGES             

  • Stem cell development or proliferation must be controlled once placed into patients.
  •  Possibility of rejection of stem cell transplants as foreign tissues is very high.
  •  Contamination by viruses, bacteria, fungi, and Mycoplasma possible.
  • Ethical debate – Harvesting ES cells destroys the blast cyst of embryo à murder

ICMR Guidelines

  • Stem cells and their derivatives fall under definition of ‘Drug’ as per the Drugs and Cosmetics Act 1940, and are categorized as ‘Investigational New Drug (IND)’ or ‘Investigational New Entity (INE)’ when used for clinical application.
  • Informed consent + video consent as per schedule Y and CDSCO  2014.
  • Need to explain about
  • Need of screening of transmittable disease
  • Procedural risk
  • Cell lines genetic manipulation and potential for commercialization.
  • Further contact in future
  • It is mandatory that the stem cells or their products/derivatives are processed in CDSCO licensed Good Manufacturing Practices (GMP) compliant facility
  • As per ICMR DBT guideline there is no approved indication for stem cell therapy as apart of routine medical practice, other than Bone Marrow and Limbal stem cell Transplantation.
  • Accordingly all stem cell therapy other than BMT shall be treated experimental. It should be conducted only as clinical trial after prior approval from Drug Controller General of India(DCGI).
  • The follow-up period should be at least two years. It could even be longer depending on the type and source of cells used, the intended clinical application and age and gender of the recipient.
  • Prohibited Area of Research
  • Human germ line gene therapy and reproductive cloning.
  •  In vitro culture of intact human embryos, regardless of the method of their derivation, beyond 14 days of fertilization or formation of primitive streak, whichever is earlier.
  • Clinical trials involving xenogeneic cells or research on Xenogeneic-Human hybrids.
  • Research involving implantation of human embryos  after in vitro manipulation, at any stage of development, into uterus in humans or primates.
  • Preclinical Safety Studies
  • Single and repeat dose toxicity studies should be performed
  • The study duration might be longer as compared to standard single dose studies for chemical entities.
  • Toxic dose and a NOAEL need to be calculated.
  •  Interaction of stem cells with drugs
  • Tumorigeneic potential should be assessed in immune-deficient mice.
  • Genotoxicity and immunogenicity need to be assessed.

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