XCell-CenterInstitute for Regenerative Medecine

Information for patientsDiabetes Mellitus treatment with autologous adult stem cells from your own bone marrow

Common Diabetes Mellitus consequences

Heart and Vascular diseasesEye and kidney complaintsWorse vascularisationDamage to nerve cells (neuropathy)Diabetic feetHigh sensibility for infectionsErectile penile dysfunction

Treatment

Too high blood glucose can lead finally to a damage ofall parts of the body. That is why it is important to treat

DiabetesMellitus type 2 or non-insulin dependentDiabetesIn this kind of disease there is a genetic component thatat about the age of 45 alters the way in which insulin isformed and as a result, insulin does not exert its action efficiently. This phenomenon is known as PeripheralInsulin Resistance, i.e. the areas where insulin has tobind to body cells (receptors) do not recognize it and asa result, insulin fails to bind or binds poorly.

Diabetes Mellitus (DM) is a group of metabolic disordersof a chronic nature characterized by a common element,hyperglycemia, which contributes to the development ofmacrovascular, microvascular and neuropathic complica-tions; thus making it one of the major causes of mortal-ity in developed or developing societies. It affects a greatnumber of people, with a 'progressive' increase of Type1 DM and an 'explosive' increase of Type 2 DM. The WHOrelates this to population growth, ageing, unhealthydiets, obesity and sedentary lifestyles. The same hap-pens with emerging Type 2DM associated with child ob-esity. All these represent very serious personal and pu- blic health problems.The cause of diabetes remains a mystery althoughgenetic and environmental factors such as obesity andlack of exercise appear to play roles.

There are two major types of diabetes:

Diabetes Mellitus type 1 or insulin dependent DiabetesIn the development of this disease, genetic, infectious andimmunologic factors are involved, which trigger the destructionof pancreatic cells in charge of producing insulin.

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Diabetes Mellitus

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the diabetes by getting the blood glucose to a normallevel. However over a longer period complications stillappear. Besides conventional treatments, stem cell therapy canbe used to treat complications (like diabetic feet) orthe insulin producing cells in the pancreas, in order toreduce insulin intake.

About Stem Cells

The discovery of the stem cell has lead to a revolution inmodern medicine. Stem cells are in fact, the "smartcells"of our bodies. These cells migrate to injured areaswithin the body and transform themselves into new tis-sue cells that replace the damaged ones. The bodyrepairs itself by continuously producing new cells and tis-sues in this manner.

Stem cells have the capacity to multiply and to renewthemselves almost indefinitely. This contrasts with nervecells, muscle cells and blood cells, which cannot multiplythemselves and have limited life spans. Stem cells canalso develop into specialized cells.

Stem cells from the bone marrow can develop into car-diac muscle, as well as liver, brain, nerve, fat and skin tis-sue. Examples of bone marrow-derived stem cell devel-opment are illustrated (right). In stroke patients thesestem cells can grow into nerve tissue, new blood vesselsthat improve circulation, or produce stimulants that acti-vate non-active insulin producing cells.

The XCell-Center Diabetes Mellitus Treatment

The entire procedure consists of the following phases:eligibility, stem cell collection and processing, stem celltreatment, and follow-up.

ObjectivesThe goal of this treatment is to repair damaged tissue orto reactivate existing cells; with the ultimate goal ofimproving vascularisation and/or reducing insulin intake.

Type of treatmentThe XCell-Stroke procedure employs autologous adultstem cells. These cells are collected from your own bone

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marrow. A few days prior to treatment, the stem cells willbe isolated from bone marrow taken from your hip (iliaccrest).

Eligibility phase

If you meet the following conditions, you are eligible fortreatment:

Stem Cell

Specialized Cell(e.g., neuron)

Stem Celle.g., hematopoietic stem cell

Liver

Brain

Blood cell

Cardiac muscle

Adult Stemcell

Skletal muscle

Bone marrow

Epithelial cell

NeuronDiabetes Mellitus type one or two diagnosis basedon your medical history, blood glucose values andimaging material such as MRI.

The XCell-Center medical team approves you fortreatment.

Your bone marrow contains a sufficient quantity ofviable stem cells. This is assessed during the pro-cessing phase.

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Arrival at XCell-Center Preparation Application of local anesthetic

Disinfection of the collection site Needle insertion into the hip bone (ileac crest)

Sample collection

Stem Cell Collection and ProcessingPrior to scheduling bone marrow collection, you will beasked to fill out the patient consent form. This formgrants explicit written permission for bone marrow col-lection.

You must discontinue using any blood diluting medica-tions at least 10 days before your collection date. Youshould consult your physician before discontinuing theuse of blood diluting drugs.

When we greet you collection day, we'll have everythingprepared to begin collection and make it comfortable foryou.

Your physician will collect approximately 150 - 200 ml ofbone marrow from your hip bone.

The pictures show Stem Cell Collection Procedure

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Stem cell collection is performed as an out-patient pro-cedure under local anesthesia in sterile conditions. It iscomparable in pain to a dentist visit. During the collec-tion, you will barely feel the needle insertion into yourhip bone. Afterwards, the collection site might look likea "blue spot" and be a bit painful for 3 - 4 days.Normally, there are no other side-effects. Theoretically,there is a small risk of infection. We minimize this risk byworking in a sterile environment.

Within 48 hours, the stem cell samples are processedand quality tested by a highly specialized laboratory intotally sterile, clean room conditions. Since they are insterile tubes and never come into contact with the air,these samples cannot be contaminated.

Bone marrow processing and quality testing consists of:

Positive isolated stem cell samples are stored in steriletubes at -196°C in liquid nitrogen.

Stem Cell Implantation

Your high-quality stem cell sample will be implanted intothe pancreas under local anesthesia using angiographyor directly injected to the damaged area.

1. Angiography

A catheter will be inserted into the femoral artery in yourpelvic region then guided to the arteries that supply thepancreas using X-ray imaging. Next, the stem cells willbe injected into each artery. Once the stem cells havebeen implanted, the doctor will remove the catheter andcompress the entry site. You will be awake during theentire procedure which takes about 1.5 hoursImmediately after treatment, you will spend about threeor four hours in our recovery room for observation.

Stem cell isolation -stem cells are separated fromthe red blood cells and blood plasma.Stem cell counting Stem cell vitality measurement

Stem cell processing results are described in ananalysis report.

The result is positive if:

There are more than two million (2,000,000) CD34+

stem cells present.The CD34+ stem cells have a vitality greater than80%

This price does not include travel expenses such asairfares and meals, or accommodation costs.

2. Direct injection

In case of treating the complications like a diabetic foot,your stem cells will be directly injected into the damagedarea. Multiple injections will be given in order to improvevasularisation.

Possible Adverse Events from the treatment

Little pain on place of injection

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Possible Adverse Events from the treatment

Bone marrow collection and transportationStem cell processing, storage and transportationStem cell administrationXCell-Center medical feesXCell-Center administrative fees

Bleeding (rare)Slight burning sensations due to contrast medium(common)Allergic reaction to contrast medium (very rare)Infarct due to dislodging of plaque within an artery(very rare)

Treatment advantages

SimpleOut patientLess bleeding risk

Follow-up

Once you have returned home, a member of our medicalteam will regularly monitor your progress via telephoneand email. For your convenience, telephone 'hotline' isalways at your disposal.

Cost

The total price for this treatment is 8.925 Euros.

This price includes:

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This price does not include travel expenses such asairfares and meals, or accommodation costs.

General

No additional charges will be incurred unless you arerequired to extend your stay at the medical center as aresult of complications. Costs do not include additionalstem cell treatments. If another treatment is necessary,we will discuss potential options with you.

You will receive an invoice one week prior to treatment.This invoice must be paid in-full before treatment canbegin.

Note: If your bone marrow sample is negative or thestem cells cannot be administered due to unforeseenmedical circumstances, you will only be required to paycharges incurred to that point. In the case of a negativebone marrow sample, it might be possible to scheduleanother bone marrow collection.

Contact:

XCell-Centerthe Institute for Regenerative Medicinec/o Eduardus-KrankenhausCustodisstraße 3-17D-50679 CologneGermany

Phone: +49221 8025095Fax: +49221 29212550

E-mail: info@xcell-center.comInternet: www.xcell-center.com

Treatment advantages

SimpleOut patientLess bleeding risk

Follow-up

Once you have returned home, a member of our medicalteam will regularly monitor your progress via telephoneand email. For your convenience, telephone 'hotline' isalways at your disposal.

Cost

The total price for the surgical treatment is 6.545 Euros.This price includes:

Bone marrow collection and transportationStem cell processing, storage and transportationStem cell administrationXCell-Center medical feesXCell-Center administrative fees