Stem Cell Technology

I. Definition
Stem cell technology is a rapidly developing field that combines the efforts of cell biologists,
geneticists, and clinicians and offers hope of effective treatment for a variety of malignant and
non-malignant diseases. Stem cells are defined as totipotent progenitor cells capable of self
renewal and multilineage differentiation.

Keypoints:

* Stem cells are progenitor cells that are capable of self renewal and differentiation into many
different cell lineages

* Stem cells have potential for treatment of many malignant and non-malignant diseases

CASE 1. COMBINATION THERAPY WITH MESENCHYMAL STEM CELLS AND

GRANULOCYTE-COLONY STIMULATING FACTOR IN A CASE OF SPINAL CORD INJURY
Introduction: Various neuroregenerative procedures (which refers to the regrowth or repair of
nervous tissues, cells or cell products) have been recently employed along with
neurorehabilitation programs to promote neurological function after Spinal Cord Injury (SCI), and
recently most of them have focused on the acute stage of spinal cord injury. In this report, we
present a case of acute SCI treated with neuroprotective treatments in conjunction with
conventional rehabilitation program.

Methods: A case of acute penetrative SCI (gunshot wound), 40 years old, was treated with
intrathecal bone marrow derived stem cells and parenteral Granulocyte-Colony Stimulating
Factor (G-CSF) which is (a class of biological medication that doctors prescribe for people who
need to boost their white blood cell count) along with rehabilitation program. The neurological
outcomes as well as safety issues have been reported.

Results: Assessment with American Spinal Injury Association (ASIA) a standardized neurological
examination used by the rehabilitation team to assess the sensory and motor levels which were
affected by the spinal cord injury)., showed neurological improvement, meanwhile he reported
neuropathic pain (The pain is usually described as a burning sensation and affected areas are
often sensitive to the touch)., which was amenable to oral medication.

Discussion: In the acute setting, combination therapy of G-CSF and intrathecal Mesenchymal
Stem Cells (MSCs) was safe in our case as an adjunct to conventional rehabilitation programs.
Further controlled studies are needed to find possible side effects and establish net efficacy.

Case presentation: A 40-year-old man was referred to our center due to complete paraplegia,
following gunshot to the left flank region since 15 days ago. In the emergency evacuation center,
he had been admitted in shock and hypovolemic state. Emergency laparotomy was performed
and revealed retroperitoneal hematoma on the left side due to the left kidney rupture,
accordingly left nephrectomy was performed at that time. After hemodynamic stabilization, a
laminectomy for dural repair was done. Upon arrival to our center the spinal X-rays revealed
stable burst fractures of T12 and L1 vertebrae associated with lateral mass fracture. There was also
a bullet in the right hemithorax subcutaneously.

Removal of the metallic bullet was easily accomplished under C-arm control before MRI
examination on the following day. Actually the bullet entry was through the left flank and it had
passed through the posterior elements of T12-L1 vertebral bodies, contusing but not passing the
spinal cord. The patient was paraplegic at T12 sensory level (AIS=A). On T2 weighted MRI, the
rostrocaudal length of signal change area was about 20 mm. Written informed consent was
obtained for both intrathecal MSCs injection and subcutaneous G-CSF administration from the
patient.
ETHICAL PRINCIPLE: The bioethical principle that is present in Case 1 is the principle of
beneficence because the healthcare team chose to do the right procedure that will save the
patient’s life and that is good for the patient.

CASE 2: PATIENT FROM DENVER USES STEM CELLS TO TREAT SEVERE NECK PAIN:
RETURNS TO GOLF, SKIING & HEALTHY SLEEP THE PATIENT PROFILE OF SEVERE
CERVICAL PAIN
The patient presented to me with a history of six months of severe right upper cervical pain. He
described his pain as sharp in character with a stabbing sensation with lateral rotation of the neck
to the right side. He was having immense difficulty with sleeping and discomfort while playing golf
or skiing.

On exam, he was tender over the upper cervical facets on the right side for C2-5. His pain was
intensified with right lateral rotation and especially if combined with extension. There was no
radiation of pain into the right upper extremity or weakness in the right arm. MRI exam
demonstrated degenerative facets on the rightmost severe at C2-C4. There were no disc
herniation or spinal stenosis of significance. Daily pain scores ranged from 3/10-7/10 and were
worst while trying to sleep.

Needle placement into the left C2-3 cervical facet joint with contrast spread throughout the joint
prior to injection of stem cell (x-ray guided stem cell neck injection).

Conservative Treatments Tried

The patient had undergone intra-articular facet injections at the right C2-5 levels with
corticosteroid which helped significantly for approximately 4 weeks before the pain returned to
pre-injection pain levels. The patient struggled with his neck pain for a while and tried many other
conservative treatments too. Those included physical therapy, massage, acupuncture,
nonsteroidal anti-inflammatory drugs, and extended resting. None of the treatments brought his
pain to tolerable levels.

Stem Cell Procedure for the Patient’s Cervical Facet Dysfunction

The decision was made to have the patient undergo intra-articular facet injections at the C2-5
levels with a combination of adipose-derived stem cells and bone marrow concentrate.

In February 2015, the patient underwent a combined procedure that included abdominal
liposuction and bone marrow aspiration. Once the cells were processed and prepared for
injection, the patient was placed in the prone position with a pillow under the chest and the head
was turned slightly to the left for best exposure to the right cervical facets.

Under fluoroscopic visualization, a 26 gauge Quincke tip needle was directed into the mid-portion
of each facet and location was verified by multi-planar fluoroscopic imaging and the use of tiny
amounts of radio-opaque contrast material. Once the needles were in optimal position an
injection of .5 cc’s of bone marrow concentrate with approximately 20 million nucleated adipose-
derived stem cells were injected into each joint without difficulty.
The patient tolerated the procedure with little discomfort and was discharged to home within four
hours in comfortable and stable condition.

Short Term Results of the Neck Pain Stem Cell Treatment

In the first 6 weeks following the stem cell therapy procedure in Denver, the patient returned to
low impact activities and pilates training. He reported very mild improvement in his pain levels and
a small amount of increased range of motion. Approximately 8 weeks following the procedure the
patient began to report significant decreases in his pain scores and most importantly,
dramatically improved sleep patterns that included longer sleep cycles without being awoken by
pain.

By the 12th week following the procedure, the patient reported 90%* improvement in his neck and
markedly improved range of motion. His sleep had returned to a virtually normal pattern that he
had not experienced in years.

Long Term Results of the Successful Treatment

The patient is now one year out from his cervical facet adipose-derived and bone marrow
concentrate stem cell procedure. He reports he continues to experience better than 90%*
improvement in his pre-injection pain scores. He has returned to playing golf without discomfort
and skiing without aggravation to his cervical facet syndrome.

He continues to be amazed at the marked improvement in his almost debilitating pain syndrome.
He reports that his only regret was not having the procedure done sooner. *Individual patient
results may vary. Contact us today to find out if stem cell therapy may be able to help you.
ETHICAL PRINCIPLE: The bioethical principles that are present in Case 2 is the principle of
beneficence and principle of veracity. Principle of beneficence because the healthcare team
chose to do the most appropriate procedure that will help ease the patient’s pain and uneasiness.
Principle of veracity because the patient told the healthcare team the truth about the
conservative treatments that he tried that didn’t work.

CASE 3: IMPROVEMENT OF BOWEL FUNCTION AFTER HUMAN UMBILICAL CORD

MESENCHYMAL STEM CELL TREATMENT FOR CROHN’S DISEASE: A CASE STUDY

Introduction
Crohn's is an Inflammatory Bowel Disease (IBD) that typically affects the terminal ileum (outer ends
of the intestines) but can affect the entire gastrointestinal tract, from mouth to anus. Left
untreated, Crohn’s Disease can result in a full-thickness inflammation in the gastrointestinal tract
causing pain, discomfort, irregular bowel movements, and digestive issues. The anti-inflammatory
properties of mesenchymal stem cells have the potential for alleviating the negative symptoms
associated with Crohn’s Disease.

Case Presentation
We report a case of a 25-year-old Caucasian American woman previously diagnosed as having
Crohn’s Disease. She had been diagnosed with Crohn’s in 2011, and was also presenting adrenal
and thyroid issues, as well as anemia related to gastrointestinal bleeding. She was treated with
human umbilical cord mesenchymal stem cell implantation protocol. This protocol consists of
implantation of 300 million human umbilical cord mesenchymal stem cells intravenously at a rate
of 1cc per minute. Three months post-treatment the patient reported significant improvement of
symptoms. During a follow up physical exam, she reported a complete reversal of her bowel and
abdominal pain symptoms, and significant improvements in energy, allowing her to return to
school for the first time in years.
Conclusions
Human umbilical cord mesenchymal stem cell implantations led to significant improvement in
bowel movements, abdominal discomfort, and blood per rectum. The subject was able to cease
steroid medications following treatment and note a sustained increase in quality of life.

Full Story
Background
Currently, there is no known cure for Crohn's Disease. Fortunately, the condition can be managed
with the proper treatment regime. Common medications used to manage Crohn's include anti-
inflammatories (steroids, etc.), painkillers, immunosuppressants (to control the body’s inflammatory
response), antibiotics, and surgery (to remove the affected area of the intestinal tract).
Unfortunately, all of these medications aim at merely reducing the severity of symptoms and can
have little effect on the underlying cause of the disease, inflammation. Also, anti-inflammatory
drugs may cause a plethora of adverse side effects, many of which can cause even more
discomfort or even induce serious complications. Stem cell therapy may help Crohn's Patients
through reduction in inflammation throughout the digestive tract, regulating the immune system
(to control immune response), and repairing injured tissue within the gastrointestinal tract. Stem
cell research has shown that cell therapy may have the ability to promote the repair of diseased,
dysfunctional or injured tissue. The therapeutic uses of stem cells as a potential therapy for a
variety of diseases have been explored immensely. The number of clinical trials conducted with
Mesenchymal Stem Cells has increased exponentially over the past few years. Stem cells have a
unique, intrinsic property that attracts them to inflammation in the body. Studies have shown that
stem cells can regenerate damaged or diseased tissues, reduce inflammation and modulate the
immune system promoting better health and quality of life. Mesenchymal stem cells (MSCs) do this
by influencing tissue repair via paracrine effects (cell signaling to change the behavior of existing
cells) or direct cell-to-cell contact.

Case Presentation
We present a 25-year old Caucasian American woman previously diagnosed with Crohn’s
Disease and having a history of postural orthostatic tachycardia syndrome (POTS), as well as
adrenal, thyroid, and anemia issues. She had been living largely without these indications until
2011 when her condition worsened, prompting medical intervention. She reported low energy,
frequent bowel movement, bloody diarrhea, abdominal pain, and cramps. She was prescribed
Decedron 0.75mg and a Remicade infusion (TNF Alpha blocker) for inflammation, as well as
medications for diarrhea, nausea, and reflux. She was also using the narcotic Norco for pain
management. The patient reported not being able to function day to day, having quit school
due to her ailments. Pre-treatment lab work was conducted to determine baseline condition. The
required labs include inflammation markers to document any abnormally high levels of
inflammation that would be expected with Crohn’s patients. Her bloodwork indicated a TNF
Alpha of 8.3 (normal range 0.0-2.2). The patient also completed a vitality questionnaire which
determined her subjective condition across 24 different overall health metrics for comparison post-
treatment. The patient did not have significant changes in blood pressure, blood oxygen level, or
body temperature during treatment. She did not report any adverse responses within 24 hours of
her treatment date. Three months post-treatment the patient reported significant improvement of
symptoms. During a follow up physical exam, she reported a complete reversal of her bowel and
abdominal pain symptoms. Her post-treatment vitality questionnaire indicated a 95%
improvement in bowel movements, abdominal discomfort, and blood per rectum, as well as a 70%
improvement in energy level. Her bowel movements had decreased from 12 to 15 per day to 1
per day, and blood per rectum from 8 to 10 per day to zero. She reported that she had not taken
Dacedron since her treatment, without any adverse effect. She had sustained higher levels of
energy, and reported that she had begun attending school once again to pursue higher
education, which was not possible prior to treatment. Six months post-treatment, the patient
underwent a colonoscopy and endoscopy with her home specialists. No signs of abnormal
inflammation of the bowel, scarring, or fistulas were noted. She had discontinued steroid use
completely as well. Patient noted sustained higher levels of energy, regular bowel movements,
and less fatigue, leading to quality of life increase.

Discussion
Crohn’s Disease affects an estimated 3.1 million adults in the United States, which show signs of
the condition, as well as IBD symptoms. While the official cause remains unknown, the symptoms
can be tied to inflammation of the gastrointestinal tract from the mouth to the anus. Symptoms
include abdominal pain, diarrhea, fever, and weight loss. It is currently believed that a
combination of environmental, immune, and bacterial factors in genetically susceptible
individuals can trigger Crohn’s Disease. Mesenchymal stem cells (MSCs) are primal or
“undifferentiated” cells. They are essentially “blank” and have the ability to become almost any
other type of cell. In the body, their function is to seek out damaged or diseased tissue and repair
or replace it. We all have a supply of stem cells when we’re born, but it decreases with time, and
their effectiveness diminishes with age. A stem cell transplant seeks to boost the body’s number of
stem cells by the hundreds of millions. Through the use of donated cord tissue-derived stem cells,
the cells used in treatment are “brand new”, with the highest potency and healing potential.
Additionally, the treatment involves only natural cell products, avoiding the use of potentially
harmful additives and drugs. Stem cells have been proven to have strong anti-inflammatory
properties. Through the use of large cell quantity transplants, the youthful stem cells have a
regulatory nature on the body. They can reduce the immuno-effect that the body cannot
regulate on its own. Specifically, MSCs can inhibit the overproduction and use of T-cells in the
body. This effect occurs without compromising the body’s natural immune system and leaving the
patient vulnerable to disease. The effect of the transplant is a return of the body to normal
immune function and a drastic reduction in a patient’s inflammation markers. This anti-
inflammatory effect can last for years at a time without the need for another transplant. What this
means for patients with autoimmune and degenerative diseases is a natural solution to their
symptoms, a respite from discomfort, and an overall increase in quality of life. Additionally, not
only will the body better be able to heal damaged tissue with the inflammation reduced, but the
stem cells will also assist is more rapid healing within the body. It is for this reason that even healthy
patients have turned to stem cell therapy as a form of “body maintenance” and to keep naturally
occurring inflammation at manageable levels.

Conclusion
Human umbilical cord stem cells have been shown to have important anti-inflammatory and
regenerative properties that have shown a positive impact on the symptoms of Crohn’s Disease
with no adverse reactions reported.
ETHICAL PRINCIPLE: The bioethical principles that are present in Case 3 is the principle of
beneficence and principle of non-maleficence because the healthcare team chose to do the
procedure that will not cause harm to the patient and will treat her disease and make her feel
relieved.