Using BMP-6 To Differentiate Adipose Derived Adult Stem Cells Into Chondrocytes And Cartilage Regeneration

Me: This post is to show that another option of growth factors we can use to turn the adipose derived adult stem cells into chondorcytes is to use BMP-6. Remember that in the long bones of adults, the marrow is considered yellow and mostly made of fatty acids. The study showed that TGF-Beta1 has also been shown to work, causing the expresion of cartilage specific genes an proteins like aggrecan and type II collagen. There was actually 5 growth factors all looked at in this study. They are looking at the chondorgenic potential of these on ADAS cells in alginate beads
  • 1. TGF-Beta 1
  • 2. TGF-Beta 3
  • 3. IGF-1
  • 4. BMP-6
  • 5. Dexamethasone
The two main points from the study are.
1. BMP-6 up-regulated AGC1 and COL2A1 expression by an average of 205-fold and 38-fold, respectively, over day-0 controls, while down-regulating COL10A1 expression by approximately 2-fold.
2. BMP-6 is a potent inducer of chondrogenesis in ADAS cells, in contrast to mesenchymal stem cells, which exhibit increased expression of type X collagen and a hypertrophic phenotype in response to BMP-6.
So for future reference, we realize that if we wanted to inject the BMP-6, we would put it in the bone marrow part, not the epiphysis part since the MSCSs only caused COL10 expression and hypertrophic phenotype. Any height increase method we create will have growth factors added in certain areas in certain combinations in certain sequences,
From PubMed study link HERE
Arthritis Rheum. 2006 Apr;54(4):1222-32.

Potent induction of chondrocytic differentiation of human adipose-derived adult stem cells by bone morphogenetic protein 6.

Estes BT, Wu AW, Guilak F.

Source

Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA.

Abstract

OBJECTIVE:

Recent studies have identified an abundant source of multipotent progenitor cells in subcutaneous human adipose tissue, termed human adipose-derived adult stem cells (ADAS cells). In response to specific media formulations, including transforming growth factor beta1 (TGFbeta1), these cells exhibit significant ability to differentiate into a chondrocyte-like phenotype, expressing cartilage-specific genes and proteins such as aggrecan and type II collagen. However, the influence of other growth factors on the chondrogenic differentiation of ADAS cells is not fully understood. This study was undertaken to investigate the effects of TGFbeta1, TGFbeta3, insulin-like growth factor 1, bone morphogenetic protein 6 (BMP-6), and dexamethasone, in various combinations, on the chondrogenic potential of ADAS cells in alginate beads.

METHODS:

The chondrogenic response of alginate-encapsulated ADAS cells was measured by quantitative polymerase chain reaction, 3H-proline and 35S-sulfate incorporation, and immunolabeling for specific extracellular matrix components.

RESULTS:

Significant differences in chondrogenesis were observed under the different culture conditions for all outcomes measured. Most notably, BMP-6 up-regulated AGC1 and COL2A1 expression by an average of 205-fold and 38-fold, respectively, over day-0 controls, while down-regulating COL10A1 expression by approximately 2-fold.

CONCLUSION:

These findings suggest that BMP-6 is a potent inducer of chondrogenesis in ADAS cells, in contrast to mesenchymal stem cells, which exhibit increased expression of type X collagen and a hypertrophic phenotype in response to BMP-6. Combinations of growth factors containing BMP-6 may provide a novel means of regulating the differentiation of ADAS cells for applications in the tissue-engineered repair or regeneration of articular cartilage.

PMID: 16572454   [PubMed – indexed for MEDLINE]    Free full text

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