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The latest research for Stem Cell Therapy and Spinal Cord Injury repair

General | June 21, 2016 | Author: The Super Pharmacist

spine, general, spinal cord injury, stem cells, sci

The latest research for Stem Cell Therapy and Spinal Cord Injury repair

The Current Approach to the Treatment of spinal cord injury includes surgery to decompress and stabilise the injury, prevention of secondary complications, management of any that do occur, and rehabilitation. Unfortunately, neurological recovery is limited, and most spinal cord injury patients still face substantial neurological dysfunction and lifelong disability.

Stem cell therapy offers several highly attractive strategies for spinal cord repair, including:

  • replacement of damaged neuronal and glial cells
  • re-myelination of spared axons
  • restoration of neuronal circuitry
  • bridging of lesion cavities
  • production of neurotrophic factors
  • anti-inflammatory cytokines
  • molecules to promote tissue sparing and neovascularisation
  • and a permissive environment for plasticity and axonal regeneration.

What Are Stem Cells?

What Are Stem Cells?Stem cells are the foundation cells for every organ and tissue in our bodies. The highly specialised cells that make up these tissues originally came from an initial pool of stem cells formed shortly after fertilisation.

Throughout our lives, we continue to rely on stem cells to replace injured tissues and cells that are lost every day, such as those in our skin, hair, blood and the lining of our gut.

Stem cells have two key properties:

1) the ability to self-renew, dividing in a way that makes copies of themselves

2) the ability to differentiate, giving rise to the mature types of cells that make up our organs and tissues.9

The two main stem cell types are:

  • embryonic stem cells (ES) cells
  • adult stem cells (i.e. somatic stem cells)

Embryonic stem cells

Embryonic stem cells have been derived from a variety of species, including humans, and are described as “pluripotent,” meaning that they can generate all the different types of cells in the body.

Embryonic stem cells can be obtained from the blastocyst (a very early embryo that has the shape of a ball and consists of approximately 150-200 cells) which is barely visible to the naked eye. At this stage, there are no organs, not even blood, just an “inner cell mass” from which embryonic stem cells can be obtained.

Human embryonic stem cells are derived primarily from blastocysts that were created by in vitro fertilisation for assisted reproduction but were no longer needed.

Adult stem cells

These are also called tissue-specific stem cells or ‘somatic’ stem cells. These types of stem cells are already somewhat specialised and can produce some or all of the mature cell types found within the particular tissue or organ in which they reside. Because of their ability to generate multiple, organ-specific, cell types, they are described as “multipotent.” In contrast to a ‘pluripotent’ stem cell, a ‘multipotent’ adult stem cell is restricted to producing cells of a certain organ or tissue type. For example, blood stem cells are multipotent cells that can produce all the different blood cell types but cannot produce the cells of other organs such as the liver or brain. Nevertheless, it is significant to note that stem cells found within the adult brain are known to be capable of making neurons and two types of glial cells, astrocytes and oligodendrocytes.

Adult stem cellsPrior to just the past decade, the prevailing view categorically denied the possibility of neurogenesis. It was universally accepted that nerve cells in the adult brain did not divide.  However, in the mid-to-late nineties, mounting scientific evidence established the fact that stem cells do occur in the adult mammalian brain and that these cells can generate into any of its three major cell lines:

  • neurons,
  • astrocytes, and
  • oligodendrocytes

Induced pluripotent stem cells (iPSC)

One of the hottest topics in stem cell research today is the study of induced pluripotent stem cells (iPSC). These are adult cells (e.g. skin cells) that are engineered, or “reprogrammed,” to become pluripotent, i.e. behave like an embryonic stem cell. Three groups of central nervous system (CNS) stem cells have been reported to date. All occur in the adult rodent brain and preliminary evidence indicates they also occur in the adult human brain.

How Could Stem Cells Contribute to Spinal Cord Repair?

A spinal cord injury involves a primary mechanical injury that directly disrupts axons, blood vessels, and cell membranes. This primary mechanical injury is followed by a secondary injury phase involving inflammation and additional cell death.

Following injury, the mammalian central nervous system fails to adequately regenerate due to intrinsic inhibitory factors expressed on central myelin and the extracellular matrix of the posttraumatic glial scar.19 

Cell-based regenerative therapySpinal cord injury has been extensively studied in many experimental animal models including mice, rats, cats, and nonhuman primates.  A combination of therapies is needed, acting at the appropriate time-point and on the correct targets. Studies in animals have shown that a transplantation of stem cells or stem-cell-derived cells may contribute to spinal cord repair by:

  • replacing the nerve cells that have died as a result of the injury
  • generating new supporting cells that will re-form the insulating nerve sheath (myelin) and act as a bridge across the injury to stimulate re-growth of damaged axons;
  • protecting the cells at the injury site from further damage by releasing protective substances such as growth factors, and soaking up toxins such as free radicals, when introduced into the spinal cord shortly after injury
  • preventing spread of the injury by suppressing the damaging inflammation that can occur after injury

Cell-based regenerative therapy

This has two primary aims:

1) to directly replace cells lost due to injury (oligodendrocytes or neurons);  

2) to influence the environment in such a way as to either enhance or support axonal regeneration, provide neuroprotection, or both. 

It is a promising strategy for spinal cord injury, and preclinical models demonstrate that cell transplantation can ameliorate some secondary events through neuroprotection and also restore lost tissue through regeneration.

Neural stem progenitor cells (NSPCs)

The transplantation of glial cells has shown great potential for remyelinating demyelinated axons and improving recovery in animal models of spinal cord injury. 

Neural stem progenitor cells (NSPCs)The isolation of adult neural stem cells in mammals was first reported in 1992. Neural stem progenitor cells (NSPCs) reside within specific niches in the adult central nervous system.

Transplantation of these NPSCs into spinal cord injury rats promoted functional recovery with neuroprotective and neuro-regenerative effects.

Most studies with transplanted NSPCs have shown modest recovery of the injured spinal cord.

Schwann cells

Schwann cells are the myelinating glia of the peripheral nervous system. The seminal work of David and Aguayo using peripheral nerve grafts provided early evidence that Schwann cells could support axonal regeneration of CNS neurons after SCI and ushered in the current era of neuro-regeneration research for SCI. The use of intact peripheral nerve segments as bridges to facilitate axonal regeneration within the injured spinal cord has continued.

Olfactory ensheathing cells (OECs)

Olfactory ensheathing cells are unique in their ability to facilitate the passage of new axons from regenerating olfactory receptor neurons (which reside in the peripheral nervous system [PNS] within the olfactory mucosa) over long distances up to a target neuron within the olfactory bulb glomeruli (CNS).

This ability to seemingly escort axons across the "PNS to CNS barrier" has made OECs an extremely attractive potential transplantation substrate in spinal cord injuries. Almost a decade of further work has curtailed the enthusiasm surrounding these cells to some extent, because it has become evident that some of the regeneration observed in OEC transplantation experiments may in fact be attributable to invading endogenous Schwann cells.

Embryonic stem cells (ESCs)

Over the past decade, significant advances have been made in the ability to preferentially drive the differentiation of ESCs into neural and specifically oligodendroglial lineages (oligodendrocyte precursor cells [OPCs]). The production of a high-purity population of OPCs from human ESCs was first achieved by researchers, Hans Keirstead and coworkers. They subsequently demonstrated that these human ESC-derived OPCs resulted in remyelination and significantly improved locomotor function when transplanted 1 week after SCI in the rat.55 Currently, this approach is being considered to begin preliminary clinical trials.  Australia’s best online discount chemist


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