Age-related osteogenic potential of mesenchymal stromal stem cells from human vertebral bone marrow

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The sequence of bone forming cell differentiation is:

 

Mesenchymal stem cells

V

Osteoprogenitors

V

Osteoblasts

 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve & db=PubMed & list_uids=1\

0404011 & dopt=Abstract

J Bone Miner Res 1999 Jul;14(7):1115-22 Related Articles, Books, LinkOut

Age-related osteogenic potential of mesenchymal stromal stem cells from human

vertebral bone marrow.

D'Ippolito G, Schiller PC, Ricordi C, Roos BA, Howard GA.

Geriatric Research, Education, and Clinical Center and Research Service,

Veterans Affairs Medical Center, Miami, Florida

33125, USA.

 

Mesenchymal stem cells (MSCs) residing in bone marrow (BM) are the progenitors

for osteoblasts and for several other

cell types.

 

In humans, the age-related decrease in bone mass could reflect decreased

osteoblasts secondary to an age-related loss of

osteoprogenitors.

 

To test this hypothesis, BM cells were isolated from vertebral bodies of

thoracic and lumbar spine (T1-L5) from 41

donors (16 women and 25 men) of various ages (3-70 years old) after death from

traumatic injury.

 

Primary cultures were grown in alpha modified essential medium with fetal bovine

serum for 13 days until adherent cells

formed colonies (CFU-Fs).

 

Colonies that stained positive for alkaline phosphatase activity (CFU-F/ALP+)

were considered to have osteogenic

potential.

 

BM nucleated cells were plated (0.5, 1, 2.5, 5, or 10 x 106 cells/10-cm dish)

and grown in dexamethasone (Dex), which

promotes osteoblastic differentiation.

 

The optimal plating efficiency using BM-derived cells from donors of various

ages was 5 x 106 cells/10-cm dish.

 

BM-derived cells were also grown in the absence of Dex at this plating density.

 

At the optimal plating density, in the presence of Dex, the number of CFU-F/ALP+

present in the BM of the younger donors

(3-36 years old) was 66.2 +/- 9.6 per 106 cells (mean +/- SEM), but only 14.7

+/- 2.6 per 106 cells in the older donors

(41-70 years old).

 

With longer-term culture (4-5 weeks) of these BM cells in medium containing 10

mM beta-glycerophosphate and 100

microg/ml ascorbic acid, the extracellular matrix mineralized, a result

consistent with mature osteoblastic function.

 

These results demonstrate that the number of MSCs with osteogenic potential

(CFU-F/ALP+) decreases early during aging in

humans and may be responsible for the age-related reduction in osteoblast

number.

 

Our results are particularly important in that the vertebrae are a site of high

turnover osteoporosis and, possibly, the

earliest site of bone loss in age-related osteoporosis.

 

PMID: 10404011 [PubMed - indexed for MEDLINE]

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Note the last sentence which ties high turnover bone sites (high death / high

replication rates) with where the earliest

signs of osteoporosis occurs.

 

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Good Health & Long Life,

Greg Watson,

http://www.ozemail.com.au/~gowatson

gowatson