Mojallal et al. Aesthetic Plast Surg.
Fat represents a potent source of autologous stem cells. Historically, the majority of research using autologous stem cells involved stem cells collected from the bone marrow. This source is associated with a painful extraction procedure and relatively low concentrations of mesenchymal stem cells. In contract, mini-liposuctions represent a less invasive extraction approach. Additionally, adipose tissue has been shown to contain substantially higher number of mesenchymal stem cells as well as hematopoietic stem cells and endothelial progenitor cells.
The use of fat derived stem cells has grown exponentially in recent years for numerous indications. Perhaps the largest data set for fat derived stem cells is possessed by Dr. Bob Harman from Vet Stem, who has treated a total of more than 10,000 large animals with this procedure. The Cellmedicine clinic has had an excellent track record of success using autologous fat for treatment of multiple sclerosis having treated more than 200 patients.
One of the major limiting factors of stem cell therapy using your own stem cells (autologous) is that the potency and number of stem cells is believed to decrease with age and disease. These studies, however, have been performed primarily from bone marrow sources of stem cells. Any hematologist will tell you that with age the bone marrow becomes drier and possesses less cells. Studies have shown that bone marrow stem cells from patients with diabetes or from obese patients have less activity as compared to age matched controls. There has been some thought that the stem cells in the adipose tissue are protected from age and disease. A current study (Mojallal et al. Influence of Age and Body Mass Index on the Yield and Proliferation Capacity of Adipose-Derived Stem Cells. Aesthetic Plast Surg. 2011 May 26) from the Service de Chirurgie Plastique, Reconstructrice et Esthétique in Lyon France sought to address this. The investigators assessed 42 women who were divided into two groups: age ≤ 40 or >40 and BMI ≤ 25 or >25. Fat tissue was harvested via manual lipoaspiration from the abdominal region. After centrifugation, 100 ml of lipoaspirate was sent to the laboratory for isolation and cultivation of ASCs. The investigators found that average cell yield was 0.380 × 10(6)/ml. Cell yield and proliferation capacity did not show statistically significant correlation to the age and BMI of patients, nor was there a statistically significant difference between cell yield and proliferation capacity between the different groups.
The study looked at some very basic parameters: cell number, viability and proliferative ability. It may be that adipose stem cells may exhibit differences in immune modulatory potential or differentiation potential between donors. This was not assessed. Additionally, the adipose derived cells were not assessed between donors suffering from different conditions. Despite these shortcomings, the data appears to support the hypothesis that adipose derived stem cells may have some advantages as compared to bone marrow stem cells, at least for autologous uses.
Mojallal et al. Aesthetic Plast Surg.
Stem cell researchers at Case Western Reserve have reported in Nature Magazine that the functional deficits caused by multiple sclerosis can be reduced by administering mesenchymal stem cell secreted factors.
While previous studies have shown promising results using mesenchymal stem cells, this is the first time that such results have been reported without using the stem cells themselves.
The Stem Cell Institute’s Founder, Neil Riordan PhD, originally cited the potential therapeutic role of mesenchymal stem cell trophic factors in the 2010 Cellular Immunology publication: Mesenchymal Stem Cells as Anti-inflammatories: Implications for Treatment of Duchenne Muscular Dystrophy
In addition to reducing functional deficits, the development of new myelinating oligodendrocytes and neurons, release of inflammatory cytokines, and suppression of immune cells influx were also observed in the Case Western study.
Details can be found here: http://www.nature.com/neuro/journal/vaop/ncurrent/full/nn.3109.html
Hepatocyte growth factor mediates mesenchymal stem cell–induced recovery in multiple sclerosis models
Lianhua Bai, Donald P Lennon, Arnold I Caplan, Anne DeChant, Jordan Hecker, Janet Kranso, Anita Zaremba Robert H Miller
Nature Neuroscience (2012) doi:10.1038/nn.3109
Received 18 January 2012 Accepted 17 April 2012 Published online 20 May 2012
Mesenchymal stem cells (MSCs) have emerged as a potential therapy for a range of neural insults. In animal models of multiple sclerosis, an autoimmune disease that targets oligodendrocytes and myelin, treatment with human MSCs results in functional improvement that reflects both modulation of the immune response and myelin repair. Here we demonstrate that conditioned medium from human MSCs (MSC-CM) reduces functional deficits in mouse MOG35–55-induced experimental autoimmune encephalomyelitis (EAE) and promotes the development of oligodendrocytes and neurons. Functional assays identified hepatocyte growth factor (HGF) and its primary receptor cMet as critical in MSC-stimulated recovery in EAE, neural cell development and remyelination. Active MSC-CM contained HGF, and exogenously supplied HGF promoted recovery in EAE, whereas cMet and antibodies to HGF blocked the functional recovery mediated by HGF and MSC-CM. Systemic treatment with HGF markedly accelerated remyelination in lysolecithin-induced rat dorsal spinal cord lesions and in slice cultures. Together these data strongly implicate HGF in mediating MSC-stimulated functional recovery in animal models of multiple sclerosis.
An interesting spinal cord injury study was published last week. The Turkish researchers tested two types of stem cells on spinal cord injured mice. The two cell types were native bone marrow cells and cultured repair stem cells called Mesenchymal stem cells. Native bone marrow cells contain bone marrow forming stem cells as well as a small number of Mesenchymal stem cells.
After injuring the spinal cords, the stem cells were implanted at the site of the injury. The control mice that received no cells had no improvement in neural activity. The mice that received both cell types had improved neural activity. The cultured Mesenchymal stem cell group improved significantly more than the native bone marrow stem cell group.
Stem Cell Rev. 2012 May 3. [Epub ahead of print]
Stem Cell Therapy in Spinal Cord Injury: In Vivo and Postmortem Tracking of Bone Marrow Mononuclear or Mesenchymal Stem Cells.
Ozdemir M, Attar A, Kuzu I, Ayten M, Ozgencil E, Bozkurt M, Dalva K, Uckan D, Kılıc E, Sancak T, Kanpolat Y, Beksac M.
School of Medicine, Department of Neurosurgery, Pamukkale University, 20070, Kinikli, Denizli, Turkey, firstname.lastname@example.org.
The aim of this study was to address the question of whether bone marrow-originated mononuclear cells (MNC) or mesenchymal stem cells (MSC) induce neural regeneration when implanted intraspinally.
MATERIALS AND METHODS:
The study design included 4 groups of mice: Group 1, non-traumatized control group; Groups 2, 3 and 4 spinal cord traumatized mice with 1 g force Tator clips, which received intralesionally either no cellular implants (Group 2), luciferase (Luc) (+) MNC (Group 3) or MSC (Group 4) obtained from CMV-Luc or beta-actin Luc donor transgenic mice. Following the surgery until decapitation, periodical radioluminescence imaging (RLI) and Basso Mouse Scale (BMS) evaluations was performed to monitor neural activity. Postmortem immunohistochemical techniques were used to analyze the fate of donor type implanted cells.
All mice of Groups 3 and 4 showed various degrees of improvement in the BMS scores, whereas there was no change in Groups 1 and 2. The functional improvement was significantly better in Group 4 compared to Group 3 (18 vs 8, p = 0.002). The immunohistochemical staining demonstrated GFP(+)Luc(+) neuronal/glial cells that were also positive with one or more of these markers: nestin, myelin associated glycoprotein, microtubule associated protein or myelin oligodendrocyte specific protein, which is considered as indicator of donor type neuronal regeneration. Frequency of donor type neuronal cells; Luc + signals and median BMS scores were observed 48-64 % and 68-72 %; 44-80 %; 8 and 18 within Groups III and IV respectively.
MSCs were more effective than MNC in obtaining neuronal recovery. Substantial but incomplete functional improvement was associated with donor type in vivo imaging signals more frequently than the number of neuronal cells expressing donor markers in spinal cord sections in vitro. Our results are in favor of functional recovery arising from both donor MSC and MNCs, contributing to direct neuronal regeneration and additional indirect mechanisms.
Spinal cord injury patient, Christina Cohen, discusses her progress after undergoing stem cell therapy at the Stem Cell Institute in Panama City, Panama. Christina suffered a T-12 injury after falling from a 150 ft cliff. Since treatment, she has regained movement, greatly reduced her dependency on drugs and regained bladder and partial bowel control.