Stem Cells & Craniofacial Bone Marrow Microenvironments - The Koh Lab at Yale School of Medicine

Transcript

• 00:05Bone marrow microenvironment
• 00:06is an extremely sophisticated
• 00:09and highly coordinated
• 00:10niche for hematopoietic stem cells.
• 00:12There are multiple components of
• 00:14this. We have blood vessels.
• 00:15We have cardiovascular cells, stromal
• 00:18cells,
• 00:19fat cells,
• 00:20nerve cells, and and so
• 00:21many more. And all these
• 00:23components
• 00:24govern
• 00:24and dictate the fate of
• 00:27an hematopoietic stem
• 00:30cell.
• 00:32Hematopoietic stem cells have the
• 00:33potential to create and regenerate
• 00:36all the blood cells in
• 00:37our body. My lab works
• 00:39on specialized
• 00:40bone marrow micro
• 00:43which govern these hematopoic stem
• 00:45cells in different cranial facial
• 00:47bones in our head.
• 00:48So before I started my
• 00:50lab,
• 00:51I discovered that the skull
• 00:52bone marrow micro environment is
• 00:54very different
• 00:55from other bone marrow compartments.
• 00:57But there are twenty three
• 00:59different cranial facial bones in
• 01:00our head. So my lab
• 01:03is trying to find out
• 01:04how functionally unique and specialized
• 01:07these bone marrow microenvironments
• 01:08are. And we're trying to
• 01:10figure out ultimately figure out
• 01:11why we have cranial facial
• 01:13bone marrow and why we
• 01:14need to have so many
• 01:15of them.
• 01:17As you know, we have
• 01:18severe bone loss during aging.
• 01:20But it's not only the
• 01:21bone that ages, the bone
• 01:23marrow also ages.
• 01:24We
• 01:25lose blood vessels in the
• 01:27bone marrow as we age.
• 01:28There's an excessive accumulation of
• 01:30fat cells, which directly inhibit
• 01:33normal hematopoic stem cell activity,
• 01:35and the environment becomes very
• 01:37inflammatory
• 01:38during aging.
• 01:40Most of these studies have
• 01:42been done in long bones
• 01:43in our arms and legs.
• 01:45And I found that the
• 01:46skull bone marrow is actually
• 01:48going in the opposite direction.
• 01:50It's actually growing and staying
• 01:52healthy in function.
• 01:57We're using innovative imaging methods
• 01:59like in vivo labeling with
• 02:00fluorescence conjugated antibodies
• 02:02to
• 02:03image these different cranial facial
• 02:05bones in its entirety.
• 02:07And we're using skull transplantation
• 02:10to assess
• 02:11specialized contribution
• 02:12from different cranial facial bones.
• 02:14We're also using intravital imaging
• 02:17to track tissue morphogenesis,
• 02:19and we're using also very
• 02:21creative methods of partial irradiation
• 02:24to assess their hematopoiet
• 02:26contribution to systemic circulation.
• 02:31Now we know that the
• 02:33skull bone marrow is continuously
• 02:35in communication with what's happening
• 02:36in the CNS in our
• 02:38brain.
• 02:39We don't know yet which
• 02:41bone marrow microenvironments are contributing
• 02:44to the neuroinflammation
• 02:46and
• 02:46subsequent neurodegeneration.
• 02:49So we're hoping to find
• 02:52novel therapeutic targets within cranial,
• 02:54facial, bone marrow that we
• 02:55could employ
• 02:57to treat neurodegenerative
• 02:59diseases like Alzheimer's or neuroinflammatory
• 03:01diseases like multiple sclerosis.